Signals of Recent Positive Selection in a Worldwide Sample of Human Populations

Supplementary information for: Signals of recent positive selection in a worldwide sample of human populations

Joseph K. Pickrell1,†, Graham Coop1,12,†, John Novembre1,2, Sridhar Kudaravalli1, Jun Li10, Devin Absher4, Balaji S. Srinivasan6,7,8,9, Gregory S. Barsh3, Richard M. Myers4, Marcus W. Feldman5, and Jonathan K. Pritchard1,11,†

1 Department of Human Genetics, The University of Chicago. 2 Department of Ecology and Evolutionary Biology, UCLA. 3 Department of Genetics, Stanford University. 4 HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL. 5 Department of Biological Sciences, Stanford University. 6 Stanford Genome Technology Center, Stanford University 7 Program in Biomedical Informatics, Stanford University 8 Dept. of Computer Science, Stanford University 9 Dept. of Statistics, Stanford University 10 Dept. of Human Genetics, University of Michigan 11 Howard Hughes Medical Institute. 12 Current Address: Department of Ecology and Evolution, University of California, Davis † To whom correspondence should be addressed: [email protected], [email protected], [email protected]

January 12, 2009

1 Power simulations. To estimate our power to detect selection in the ascertained Illumina data, we performed simulations under the “cosi” model of human demography [3] with a slight modification– for computational efficiency, the recent increases in population size were dropped. This had little effect on the fit of the model to the HapMap data (results not shown). Other rele- vant parameters are described in the main text. The selection model is one where a single selected site arises and sweeps up in frequency. Implicitly, this assumes a given selected locus in the human genome has experienced only a single selective sweep in the time from over which our statistics are applicable (approximately 10-80ky); we find this reasonable, and simulations of this kind are a standard method for testing the power of a test for selection [2, 4–7] To approximate the ascertainment of the Illumina panel, we performed a two-stage ascertainment on all of the simulations; this is described in the main text. In Supplementary Figure 1, we show that this procedure provides a good approximation to the frequency spectrum of the Illumina chip. For calculations of power, in all cases the selected site was excluded from analysis, making the calculations conservative. In Supplementary Figure 2, we show power estimates as a function of derived allele frequency in different demographies, and in Supplementary Figure 3, we show the effect of sample size on power. About 200 of the simulations have a selected allele that arises on the branch common to both the “European” and “Asian” populations; this allows us to get an upper bound on the expected amount of overlap between the populations for XP-EHH (with a selection coefficient of 1% almost all selected alleles that arose during that branch would have gone to fixation and are not likely to be detected by iHS). In these simulations of truly shared selective sweeps, 76% are detected in both populations.

Overlap of haplotype-based selection signals between populations. We calculated iHS and XP-EHH in each individual population, and converted scores to empirical p-values as described in the text. For a signal to be considered overlapping between populations, we required that the iHS or XP-EHH score be in the 1% tail of one population and the 5% tail of the other. In Supplementary Figures 4 and 5, we show the fraction of selection signals that overlap between all pairs of populations. The striking diﬀerence between African and non-African populations in XP-EHH is an artifact of the way XP-EHH is calculated–for non-African populations, we used the group of Bantu speakers as a reference, and for African populations we used a group of European chromosomes as the reference. We performed the test this way to most closely follow what was most powerful in the simulations, but this means that the non-overlap between African and non-African populations by XP-EHH is not meaningful.

Calculation of the CLR statistic and overlap with other signals of selection The CLR test used in the main text as an alternative to XP-EHH for detecting high-frequency sweeps was originally designed to be applied to data for which SNP ascertainment is constant across the genome and, ideally, can be properly modeled. This is not the case for the HGDP data–tag SNPs were identiﬁed in the HapMap database, which has complicated and often unknown ascertainment [1].

2 Because of this, we have used this statistic not as a formal test for significance, but rather to rank regions by the deviance of the allele frequency spectra from the genome-wide average. We then used the CLR statistics as test statistics like XP-EHH and iHS and convert them to empirical p-values after controlling for SNP density, as described in the main text. As XP-EHH and CLR both detect local deviations in the allele frequency spectrum (XP-EHH detects regions of extended homozygosity), we expect them to largely overlap. This is indeed the case for non-African populations–defining overlap as above, we find that the CLR and XP-EHH statistics overlap 63%, 58%, 67%, 83%, 88%, and 71% for Europe, the Middle East, S. Asian, E. Asia, Oceania, and the Americas, respectively. For the Bantu, however, the overlap is only 28%. We interpret this to mean that many signals of fixed sweeps in the Bantu are less robust than those outside of Africa. This is consistent with the observation that there appear to be few reliable signals of recent fixations in African populations[2, 4].

3 Unascertained simulations Ascertained simulations Illumina ASN YRI Density CEU

0 1 0 1 0 1 Derived allele frequency

Figure 1: Marginal frequency spectra in the simulations before and after the application of the ascertainment procedure, as well as in the real data. In the ﬁrst column are the marginal allele frequency spectra in the simulations before application of the ascertainment procedure, in the second column are the allele frequency spectra in the simulations after the application of the ascertainment procedure, and in the third column are the marginal allele frequency spectra in the HapMap populations at the SNPs typed on the Illumina panel.

4 1.0 A 1.0 B 0.8

0.8 YRI 0.6 0.6 YRI Power CEU Power 0.4

CEU 0.4 ASN ASN 0.2 0.2 0.0

0.2 0.4 0.6 0.8 1.0 0.0

Derived allele frequency 0.2 0.4 0.6 0.8 1.0

Derived allele frequency

Figure 2: Power of iHS (A) and XP-EHH (B) in three demographies based on the HapMap. Selected alleles were introduced at a random time with a selection coeﬃcient of 1% and simulated forwards in time. In all simulations, the selected site was excluded from analyses. Simulations were binned into six bins according the the ﬁnal frequency of the selected allele. The type I error was set to 1%, with the threshold determined by neutral simulations.

5 A B

1.0 n = 120 1.0 n = 120

● 100 100 ● ● ●

0.8 80 0.8 80 ● 40 40 ● 20 20 ●

0.6 ● 0.6 ● ● Power Power ● ●

0.4 ● 0.4 ● ● ● ● ● ● ● ● ● ● 0.2 0.2 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 0.0 0.0

0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0

Derived allele frequency Derived allele frequency

Figure 3: Power of iHS (A) and XP-EHH (B) in the YRI demography for different sample sizes (in number of chromosomes). Selected alleles were introduced at a random time with a selection coefficient of 1% and simulated forwards in time. Simulations were binned into six bins according the the final frequency of the selected allele. The type I error was set to 1%, with the threshold determined by neutral simulations.

6 BantuKenya BantuSouthAfrica Yoruba San Mandenka MbutiPygmy BiakaPygmy Orcadian Adygei Russian Basque French Italian Sardinian Tuscan Mozabite Bedouin Druze Palestinian Balochi Brahui Makrani Sindhi Pathan Burusho Hazara Uygur Kalash Han Han.NChina Dai Daur Hezhen Lahu Miao Oroqen She Tujia Tu Xibo Yi Mongola Naxi Cambodian Japanese Yakut Melanesian Papuan Karitiana Surui Colombian Maya Pima 100% BantuKenya BantuSouthAfrica Yoruba San Mandenka MbutiPygmy BiakaPygmy Orcadian Adygei Russian Basque French Italian Sardinian Tuscan Mozabite Bedouin Druze Palestinian Balochi Brahui Makrani Sindhi Pathan Burusho Hazara Uygur Kalash Han Han.NChina Dai Daur Hezhen Lahu Miao Oroqen She Tujia Tu Xibo Yi Mongola Naxi Cambodian Japanese Yakut Melanesian Papuan Karitiana Surui Colombian Maya Pima

Figure 4: Overlap of iHS signals across populations. In each cell (i, j) the fraction of windows with scores in the 1% tail of iHS in population i and in the 5% tail of iHS in population j is colored according the legend on the right.

7 BantuKenya BantuSouthAfrica Yoruba San Mandenka MbutiPygmy BiakaPygmy Orcadian Adygei Russian Basque French Italian Sardinian Tuscan Mozabite Bedouin Druze Palestinian Balochi Brahui Makrani Sindhi Pathan Burusho Hazara Uygur Kalash Han Han.NChina Dai Daur Hezhen Lahu Miao Oroqen She Tujia Tu Xibo Yi Mongola Naxi Cambodian Japanese Yakut Melanesian Papuan Karitiana Surui Colombian Maya Pima 100% BantuKenya BantuSouthAfrica Yoruba San Mandenka MbutiPygmy BiakaPygmy Orcadian Adygei Russian Basque French Italian Sardinian Tuscan Mozabite Bedouin Druze Palestinian Balochi Brahui Makrani Sindhi Pathan Burusho Hazara Uygur Kalash Han Han.NChina Dai Daur Hezhen Lahu Miao Oroqen She Tujia Tu Xibo Yi Mongola Naxi Cambodian Japanese Yakut Melanesian Papuan Karitiana Surui Colombian Maya Pima

Figure 5: Overlap of XP-EHH signals across populations. In each cell (i, j) the fraction of windows with scores in the 1% tail of XP-EHH in population i and in the 5% tail of XP-EHH in population j is colored according the legend on the right.

8 nlgu oFgr ntemi et u ssasiigwno f20bta ldsi tp of steps in slides that 200kb of window sliding a uses but text, main the in 100kb. 1 Figure to analogous 6: Figure o 0iS()adX-H B inl ypplto cluster population by signals (B) XP-EHH and (A) iHS 10 Top

BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001 0.001 chr9 31.1:31.6 chr7 106.1:106.4 PIK3CG chr7 66.5:67.1 chr10 9.5:9.9 chr4 33.7:34.3 chr17 0.4:0.9 VPS53,FAM57A,C17orf25,RNMTL1,NXN,TIMM22,ABR,GEMIN4 chr3 29.3:29.8 RBMS3 chr2 80:80.3 CTNNA2 chr3 133.1:133.4 CPNE4 chr4 130.1:130.4 SCLT1,C4orf33 chr6 164.5:164.8 chr2 84.2:84.5 LOC388965 chr8 106.4:106.7 ZFPM2 chr5 108.9:109.3 MAN2A1 chr9 115:115.3 RGS3,SLC31A1,CDC26,PRPF4,RNF183,WDR31,BSPRY,HDHD3,ALAD,POLE3,C9orf43 chr15 69.9:70.1 MYO9A chr11 18.5:18.8 TSG101,SPTY2D1,TMEM86A,IGSF22,PTPN5,UEVLD chr19 43.3:43.6 SIPA1L3,DPF1,PPP1R14A,SPINT2,LOC541469,C19orf33,YIF1B,KCNK6,C19orf15,PSMD8,GGN,SPRED3,RASGRP4,FAM98C chr14 100.2:100.5 C14orf70,DLK1 chr11 109.8:110.3 FDX1,ARHGAP20 chr13 87.8:88.1 chr16 86.3:86.6 KLHDC4,SLC7A5,CA5A,BANP chr16 79.9:80.2 GAN,CMIP chr14 84.5:84.8 chr9 11.8:12.1 chr20 34.8:35.1 NDRG3,DSN1,C20orf117,C20orf118,SAMHD1,RBL1 chr3 100.8:101.1 COL8A1,FLJ44076,C3orf26,FILIP1L chr1 207:207.3 ANP32B,C9orf156,FOXE1,HEMGN,NANS,TRIM14 chr9 99.6:99.9 chr13 24.1:24.4 ATP12A,CENPJ,RNF17 chr18 40.8:41.2 SETBP1 chr6 75.3:75.6 chr2 59:59.3 chr14 97.5:97.8 chr19 46.9:47.3 POU2F2,CEACAM6,LYPD4,RPS19,ARHGEF1,RABAC1,ATP1A3,GRIK5,ZNF574,DMRTC2,CEACAM5,CEACAM3,CD79A chr17 60.5:60.9 RGS9 chr10 12.3:12.6 CDC123,CAMK1D chr2 167.6:168 CMYA3 chr15 46:46.5 SLC24A5,MYEF2,SLC12A1,DUT,FBN1 chr4 60.5:61.1 chr21 16.2:17.1 C21orf34 chr9 106.9:107.2 SLC44A1 RGS9,AXIN2 chr14 60.8:61.3 TMEM30B,PRKCH,HIF1A,SNAPC1 chr17 60.5:61 chr9 3.1:3.5 RFX3 chr9 90:90.4 SPIN1,C9orf121 chr7 119.8:120.3 KCND2,TSPAN12 chr8 139.7:140.3 COL22A1 chr3 131.4:131.9 FLJ35880,PIK3R4 chr3 131.3:131.8 FLJ35880 chr8 139.5:139.9 C8ORFK32,COL22A1 chr10 65.4:65.8 chr5 19.6:20.1 CDH18 chr18 64.7:65 CCDC102B chr18 11.1:11.4 APBA2 chr5 26.3:26.8

9 chr15 27:27.2 chr15 45.9:46.5 SLC24A5,MYEF2,SLC12A1,DUT,FBN1 chr20 52.3:52.7 DOK5 chr14 62.5:63.1 KCNH5,RHOJ,GPHB5,PPP2R5E chr17 56:56.7 PPM1D,BCAS3 chr17 50.9:51.4 TMEM100,PCTP chr14 62.6:63.1 KCNH5,RHOJ,GPHB5,PPP2R5E chr8 10.9:11.4 C8orf15,MTMR9,AMAC1L2,C8orf13,BLK,XKR6 chr6 0:0.3 DUSP22,FLJ43763 0.05 chr9 122.6:123.1 PSMD5,PHF19,TRAF1,C5,CEP110,RAB14,GSN 0.05 chr3 25.8:26.1 OXSM chr12 87.1:87.9 TMTC3,KITLG chr11 87.1:87.4 chr7 119.4:119.9 KCND2 chr22 44.9:45.2 FLJ20699,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1 chr3 176.6:177 NAALADL2 chr2 108.8:109.1 FLJ32745,EDAR chr4 29.3:29.9 chr5 112.2:112.7 APC,SRP19,DCP2,MCC,REEP5 chr11 25.1:25.7 chr6 125.8:126.3 HEY2,NCOA7 chr2 212.6:213.3 ERBB4 chr15 61.4:61.9 CA12,USP3,FBXL22,HERC1 chr10 94.8:95.2 EXOC6,CYP26C1,CYP26A1,FER1L3 chr2 177:177.5 chr16 78.3:78.6 chr4 41.3:41.9 DKFZP686A01247,PHOX2B,TMEM33,WDR21B,SLC30A9,CCDC4 chr10 55.5:55.9 PCDH15 chr22 21.5:21.9 RTDR1,GNAZ,RAB36,BCR chr11 25.1:25.6 chr8 138.9:139.3 C8ORFK32 chr20 33.5:33.7 CEP250,ERGIC3,SPAG4,CPNE1 VSNL1 chr3 67.5:67.9 SUCLG2 chr2 17.1:17.7 chr8 63.8:64.1 FAM77D,GGH,FLJ39198 chr22 44.7:45.3 FLJ20699,WNT7B,FLJ27365,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1,C22orf26 chr2 165.1:165.6 GRB14,COBLL1,FLJ39822 chr6 105.1:105.7 HACE1,LIN28B,BVES chr8 63.2:63.7 FAM77D chr8 19.4:19.9 ChGn,INTS10,LPL FBXO43,RGS22,POLR2K,SPAG1,RNF19 chr8 101.1:101.5 chr5 58.5:59.1 PDE4D chr2 2.7:3 chr2 125.9:126.2 chr4 94.9:95.5 GRID2,ATOH1,SMARCAD1,PGDS chr14 69.4:69.7 SMOC1,SLC8A3 chr8 100:100.5 OSR2,VPS13B chr16 77.2:77.6 WWOX chr6 105.8:106.1 PREP chr2 165.8:166.3 SCN2A,FAM130A2 chr12 65.6:66.1 CAND1 PKIB,FABP7,SMPDL3A chr6 122.9:123.2 chr1 174.7:175.3 ASTN1,PAPPA2 chr16 10.9:11.5 PRM1,CIITA,DEXI,KIAA0350,SOCS1,TNP2,PRM3,PRM2,C16orf75,LOC400499 chr2 161.2:161.7 chr2 177.7:178.3 HNRPA3,PDE11A,NFE2L2,AGPS,TTC30A,TTC30B chr8 33.4:33.7 FUT10,RBM13,C8orf41,RNF122,DUSP26 chr22 46.3:46.7 FLJ46257 chr6 47.6:47.9 GPR115,OPN5,GPR111,CD2AP chr10 59.1:59.5 chr10 110:110.2 chr2 178.4:178.9 DRB1,PDE11A,OSBPL6 chr12 30.7:31.1 IPO8,C1QDC1,TSPAN11 chr4 158.1:159.1 PDGFC,GLRB,GRIA2 chr6 122.6:122.8 HSF2 chr12 125.3:125.8 chr4 68.5:68.9 TMPRSS11A,TMPRSS11F,CHR415SYT,TMPRSS11B,YTHDC1 chr1 159.8:160.2 FCGR2C,FCGR3B,FCGR2B,FCRLA,FCRLB,DUSP12,ATF6 chr2 158.2:158.7 ACVR1,UPP2 hsis This . nlgu oFgr ntemi et u ssawno ieo 100kb. of size window a uses but text, main the in 1 Figure to analogous 7: Figure o 0iS()adX-H B inl ypplto cluster population by signals (B) XP-EHH and (A) iHS 10 Top

BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001 0.001 chr9 31.2:31.6 chr7 66.6:67 chr11 34.3:34.4 ABTB2 chr2 97.6:97.8 COX5B,ACTR1B,ZAP70 chr10 9.6:9.8 chr5 109:109.2 MAN2A1 chr19 56.8:56.9 SIGLEC5 chr6 26.4:26.6 BTN3A2,BTN2A2,BTN3A1,BTN2A3,BTN3A3,BTN2A1 chr19 52.2:52.4 GRLF1,NPAS1,TMEM160,SAE1 chr3 29.4:29.8 RBMS3 chr7 106.2:106.3 PIK3CG chr11 57.8:58 OR5B17,OR5B3,OR5B2,OR5B12 chr2 80.1:80.2 CTNNA2 chr3 133.2:133.4 CPNE4 chr17 0.6:0.8 C17orf25,RNMTL1,NXN,GEMIN4 chr6 85.4:85.6 TBX18 chr11 29.9:30 KCNA4 DCAMKL1 chr13 35.4:35.6 chr13 107.7:107.8 TNFSF13B chr19 43.4:43.6 DPF1,PPP1R14A,SPINT2,LOC541469,C19orf33,YIF1B,KCNK6,C19orf15,PSMD8,GGN,SPRED3,RASGRP4,FAM98C chr9 11.8:12 chr6 164.6:164.7 chr11 109.8:110.2 FDX1,ARHGAP20 chr14 84.6:84.7 chr14 97.6:97.8 chr20 34.9:35 C20orf117,C20orf118,SAMHD1 chr10 20.4:20.6 PLXDC2 chr13 24.2:24.3 RNF17 chr11 9.8:10.2 SBF2 chr19 47:47.2 LYPD4,RPS19,ARHGEF1,RABAC1,ATP1A3,GRIK5,DMRTC2,CEACAM3,CD79A chr9 99.6:99.8 ANP32B,C9orf156,FOXE1,HEMGN chr2 59.1:59.2 chr16 22.8:23 HS3ST2,USP31 chr11 63:63.2 HRASLS5,LGALS12,RARRES3,HRASLS2,HRASLS3,DKFZP564J0863 chr4 119.8:120 KIAA1627,SEC24D chr10 12.4:12.5 CAMK1D chr2 167.6:168 CMYA3 chr1 207.1:207.2 RGS9 chr17 60.6:60.8 chr20 16.4:16.5 C20orf23 chr9 107:107.2 SLC44A1 chr17 60.6:60.9 RGS9 chr14 60.8:61.2 TMEM30B,PRKCH chr4 60.6:61 chr17 56.1:56.4 BCAS3 chr9 3.2:3.4 RFX3 chr15 46.2:46.5 SLC24A5,MYEF2,SLC12A1,DUT,FBN1 chr3 131.4:131.8 FLJ35880 chr17 56.2:56.7 BCAS3 chr3 25.8:26 OXSM chr8 140:140.2 chr2 178:178.2 AGPS,TTC30A,TTC30B,PDE11A chr5 74.8:75.1 COL4A3BP,POLK,C5orf37 chr2 212.8:213.2 ERBB4 chr10 65.4:65.7 chr4 34:34.2 chr18 11.2:11.3 chr14 62.6:63 KCNH5,RHOJ,GPHB5,PPP2R5E chr9 90.1:90.4 SPIN1,C9orf121 10 chr5 19.6:20 CDH18 chr22 45:45.2 FLJ20699,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1 chr8 139.6:139.8 COL22A1 chr12 87.6:87.9 chr15 27:27.2 APBA2 chr14 62.8:63.1 RHOJ,GPHB5,PPP2R5E chr7 119.8:120.2 KCND2 COMMD3,BMI1,SPAG6 chr15 46:46.4 SLC24A5,MYEF2,SLC12A1 chr10 22.4:22.7 0.05 chr17 51:51.4 TMEM100,PCTP 0.05 chr15 46.6:46.8 FBN1 chr8 11:11.2 C8orf15,MTMR9,XKR6 chr5 26.5:26.7 chr22 45:45.2 FLJ20699,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1 chr21 16.7:17 C21orf34 chr10 83.8:84.2 NRG3 chr17 50.9:51.1 chr6 73.8:74 KCNQ5 chr4 29.5:29.7 chr2 108.8:109 FLJ32745,EDAR chr3 176.7:176.9 NAALADL2 chr6 125.8:126.2 HEY2,NCOA7 chr7 119.6:119.9 KCND2 SULT1C3,SULT1C1,SULT1C2 chr2 108:108.4 chr22 21.6:21.8 RTDR1,GNAZ chr10 55.6:55.8 PCDH15 chr11 25.3:25.6 chr10 94.8:95.2 EXOC6,CYP26C1,CYP26A1,FER1L3 chr5 112.2:112.6 APC,SRP19,DCP2,MCC,REEP5 chr4 158.7:159 chr10 55:55.2 chr15 61.6:61.9 USP3,FBXL22,HERC1 chr11 25.2:25.6 chr2 177.2:177.5 chr12 1.2:1.4 ERC1 chr4 41.7:41.9 SLC30A9,CCDC4 chr8 63.8:64 FAM77D chr2 17.6:17.9 VSNL1,SMC6,FLJ40869 chr3 67.6:67.8 SUCLG2 chr21 16.3:16.6 C21orf34 chr2 165.2:165.6 COBLL1,FLJ39822 chr6 105.2:105.5 HACE1 chr2 126:126.2 chr5 58.9:59.2 PDE4D chr14 69.4:69.6 SMOC1,SLC8A3 chr8 19.5:19.8 ChGn,INTS10 chr5 61.2:61.4 chr12 65.7:66 CAND1 chr6 29.4:29.6 OR5V1,OR12D3,OR12D2,OR11A1,OR10C1,OR2H1,MAS1L chr4 95.2:95.5 SMARCAD1,PGDS chr3 162.6:162.8 LOC131149 chr12 92.8:93 chr8 100.2:100.5 VPS13B chr2 165.8:166.2 SCN2A,FAM130A2 chr5 58.6:58.8 PDE4D chr16 11:11.4 PRM1,KIAA0350,SOCS1,TNP2,PRM3,PRM2,C16orf75 chr6 105.8:106 PREP chr2 161.2:161.6 chr10 59.2:59.4 chr6 47.6:47.8 GPR115,GPR111,CD2AP chr12 125.4:125.6 chr10 110:110.2 chr2 177.9:178.2 AGPS,TTC30A,TTC30B,PDE11A chr12 30.8:31 TSPAN11 chr2 158.4:158.6 ACVR1,UPP2 chr6 122.6:122.8 HSF2 chr2 178.3:178.6 PDE11A chr13 87.8:88.2 chr22 46.4:46.7 FLJ46257 C5orf16,FCHSD1,CENTD3 chr5 141:141.2 chr16 11.1:11.4 PRM1,KIAA0350,SOCS1,TNP2,PRM3,PRM2,C16orf75 chr4 68.6:68.8 TMPRSS11F,CHR415SYT,TMPRSS11B chr4 158.2:158.4 GLRB,GRIA2 chr8 33.4:33.6 FUT10,RBM13,C8orf41,RNF122,DUSP26 hsis This . BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001 chr10 106.6:106.8 SORCS3 chr2 81.8:82.2 chr11 55:55.6 OR4C15,OR4C11,OR4P4,OR4C6,OR5D13,OR5D14,OR5L1,OR5D18,OR5L2,OR5D16,SPRYD5,OR5W2,OR5I1,OR10AG1,OR5F1,OR5AS1,OR4C16,OR4S2 chr7 117.6:118 ANKRD7,LSM8 chr11 61.2:61.4 C11orf11,C11orf9,C11orf10,FEN1,FADS1,FADS2,FADS3 chr7 106.6:107 HBP1,COG5,DUS4L,GPR22 chr5 75.4:75.6 SV2C chr11 56:56.2 OR5M8,OR5M11,OR5M10,OR5M1,OR5AP2,OR5AR1 chr10 64.6:65 JMJD1C,REEP3 chr7 127.2:127.4 SND1 chr5 158.4:158.6 EBF1,FLJ31951 chr12 85.8:86.2 chr2 50.8:51 NRXN1 chr1 113.6:114 MAGI3 chr20 17.4:17.6 PCSK2,BFSP1,DSTN,RRBP1 chr6 100.8:101 SIM1 chr19 47:47.6 POU2F2,LYPD4,RPS19,ARHGEF1,RABAC1,ATP1A3,GRIK5,ZNF574,DEDD2,ZNF526,GSK3A,ERF,PAFAH1B3,MGC70924,MEGF8,C19orf49,CNFN,LIPE,CIC,TMEM145,DMRTC2,CEACAM3,CD79A chr14 62.8:63 RHOJ,GPHB5,PPP2R5E chr13 33:33.4 RFC3 chr15 67.4:67.8 PAQR5,KIF23,RPLP1,LOC729416 chr3 190:190.4 LPP,FAM79B chr5 11.6:12 CTNND2 chr5 109.6:110.2 SLC25A46 chr6 128.6:129 PTPRK chr2 21.4:21.8 chr18 30.4:30.6 DTNA chr13 103.6:103.8 chr1 35.2:36 SFPQ,ZMYM4,KIAA0319L,NCDN,TFAP2E,PSMB2,FLJ38984,CLSPN,ZMYM1,ZMYM6 chr15 46:46.4 SLC24A5,MYEF2,SLC12A1 chr8 24:24.4 ADAM7,ADAM28,ADAMDEC1 chr12 87.4:88 KITLG chr5 111.6:111.8 EPB41L4A chr21 16.6:17 C21orf34 chr3 98.4:98.8 EPHA6 0.05 chr9 32.6:32.8 TAF1L,LOC401498 chr17 55.6:56.4 USP32,C17orf64,APPBP2,PPM1D,BCAS3 chr7 119.4:120 KCND2 chr5 117.4:117.8 chr4 41.4:42 PHOX2B,TMEM33,WDR21B,SLC30A9,CCDC4 chr2 177.2:177.6 chr3 108.6:109.2 BBX chr15 61.6:62.2 USP3,FBXL22,HERC1,DAPK2,FAM96A,SNX1 chr8 10.8:11.2 C8orf15,MTMR9,XKR6 chr1 103.2:103.6 COL11A1 chr3 25.6:26.2 RARB,TOP2B,NGLY1,OXSM chr8 138.8:139.2 chr8 63.2:64.4 YTHDF3,FAM77D,GGH,TTPA,FLJ39198 chr4 159.2:160 C4orf18,TMEM144,RXFP1,LOC201725,PPID,ETFDH chr10 44:44.2 CXCL12 chr5 58.8:59.2 PDE4D chr2 151.6:152 RBM43,NMI,TNFAIP6,RIF1 chr10 110.2:111.2 chr4 160.2:160.6 chr9 0.8:1 DMRT1,DMRT3 chr8 9.8:10.2 MSRA chr4 170.4:171.2 SH3RF1,NEK1,CLCN3,C4orf27,MFAP3L chr10 59.2:59.6 chr2 177.8:178.4 PDE11A,NFE2L2,AGPS,TTC30A,TTC30B chr1 50.8:51.6 C1orf34,FAF1,CDKN2C,RNF11,EPS15 chr6 122:122.4 chr2 158.8:159.4 LOC130940,PKP4,LOC92196 chr3 157.4:157.8 KCNAB1,SSR3 chr6 35.2:35.6 TCP11,SCUBE3,ZNF76,DEF6,FANCE,RPL10A,TEAD3,TULP1,PPARD chr12 125.4:125.8 chr6 49.4:49.8 MUT,CENPQ,C6orf141,RHAG,CRISP2 chr5 155:155.4

Figure 8: Top 10 CLR signals by population cluster. This is analogous to Figure 1 in the main text.

11 Africa−Europe Africa−E.Asia 1200 1200 800 800 Counts Counts 400 400 PJ G L NCIRJF M 0 SFIORKBAMECDHQN 0 SAOEDQKPH GBL

Europe−E.Asia S.Asia−E.Asia 1500 1500 1000 Counts Counts Counts 500 500 AOSBFHC K R PSBAQK 0 RJ LNPIGEMDQ 0 OIFGJHCDNLEM

Africa−S.Asia Europe−S.Asia 1500 A CETP K LPL_2 B LPL L SORT1 C LIPC M PDSK9

1000 D ABCA1

1500 N GALNT2 E LIPG O MVK F APOC_clust

Counts Counts P NCAN G APOB 500 H LDLR Q TRIB1 R MLXIPL

500 I APOA_clust P Q KFHGDC J GCKR S ANGPTL3 0 SI J FNORADCEKMGBLH 0 REBOSPAMLNJI Q 0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0

FST Fst FST

Figure 9: FST surrounding loci involved in natural variation in lipid levels. This ﬁgure was generated as in Figures 3 and 4 in the main text.

12 Africa−Europe Africa−E.Asia 1200 1200 800 800 Counts Counts 400 400 D1KWTI 42H WOK2G3 0 CYPAOLRGZSVNXQMBUE3J F 0 ZYFMSPDVXT1HR4QLUIJENACB

Europe−E.Asia S.Asia−E.Asia 1500 1500 1000 Counts Counts Counts 500 500 2WS3VKB4TZG E 2SHEIAB4FZQCLG 0 MIXHYP1LAQOCFRUJD N 0 MKW3VOXDPRYJUT1 N

Africa−S.Asia Europe−S.Asia 1500 A IL23R K PTPN2 U 8q24 B ATG16L1L PTPN22 V JAK2 C MST1 M ITLN1 W 10p11

1000 D PTGER4 N 1q24 X C11orf30 1500 E 5q31 O 1q32 Y LRKK2 F IRGM P IL12B Z 13q14 Counts Counts G TNFSF15Q CDKAL1 1 ORMDL3 500 H ZNF365 R 6q21 2 STAT3 21q21 500 I NKX2−3 S CCR6 3 YDNTSXMUKHBA2 1QCXSDUO J NOD2 T 7p12 4 ICOSLG 0 CGPLZ1VOWR4QI EJ3F 0 W3PB2YZ4MFLGHRIVATKNJE 0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0

FST Fst FST

Figure 10: FST surrounding loci involved in natural variation in susceptibility to Crohn’s disease. This ﬁgure was generated as in Figures 3 and 4 in the main text.

13 Africa−Europe Africa−E.Asia 1200 1200 800 800 Counts Counts 400 400 I DO1RJfHZegWP c JgLh9Z c a 0 TCNLFh5MQXdEY6GB8U47V9A 3KSb2 a 0 I 1dM3TPWONBQH6K5E8f7DCXVReUGYbA4S2 F

Europe−E.Asia S.Asia−E.Asia FST 1500 1500 1000 Counts Counts Counts 500 500 7Uag28KcNRQe9G4CB 7gd52D6fNEC39LGSe 0 IhH5EDZLdfTM1OWJ63VSXbPAY F 0 hUIHaMO8PcTW1RVZJQXK4YAFb B

Africa−S.Asia Europe−S.Asia 1500

A ZBTB38 P ADAMTSL3 5 PLAG1 B CDK6 Q IHH 6 8q21 C HMGA2 R CEP63 7 ZNF462 D GDF5 S ACAN 8 14q32 E LCORL T DYM 1000 9 F LOC387103 U 1q12 ADAMTS17 1500 G EFEMP1 V DNM3 a 17q11 H C6orf106 W C1orf19 b 17q23A I PTCH1 X BMP6 c 17q23B Counts Counts J SPAG17 Y 6p22 d 18q11

500 K SOCS2 Z BAT3 e BMP2 L HHIP 1 TNXB f LIN28B M ZNF678 2 6p21E 500 g N DLEU7 3 GPR126 DOTL1 g h CDCHD7 MCd5Rfe8VZHF74U 2b HM3VNWAdUIO8cX42CY1 O SCMH1 4 GNA12 0 T1INPDhOJBGWQYXL9E6 SK3Ac a 0 7hT5KfEbZJRGDaQSg6e9BFLP 0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0

FST Fst FST

Figure 11: FST surrounding loci involved in natural variation in height. This ﬁgure was generated as in Figures 3 and 4 in the main text.

14 Pygmy−Bantu

A ZBTB38 P ADAMTSL3 5 PLAG1 2500 B CDK6 Q IHH 6 8q21 C HMGA2 R CEP63 7 ZNF462 D GDF5 S ACAN 8 14q32 2000 E LCORL T DYM 9 ADAMTS17 F LOC387103 U 1q12 a 17q11 G EFEMP1 V DNM3 1500 H C6orf106 W C1orf19 b 17q23A

I PTCH1 X BMP6 c 17q23B Counts J SPAG17 Y 6p22 d 18q11 1000 K SOCS2 Z BAT3 e BMP2 L HHIP 1 TNXB f LIN28B a M ZNF678 2 6p21E 500 OMKg I Bc AYe9 g DOTL1 NFZCJhb 8 2D N DLEU7 3 GPR126 GQfHS L h CDCHD7 P3E17U6WT R O SCMH1 4 GNA12 0 5 4 VX d

0.0 0.2 0.4 0.6 0.8 1.0

FST

Figure 12: FST between Bantu and Pygmy populations surrounding loci involved in natural variation in height. This ﬁgure was generated as in Figures 3 and 4 in the main text.

15 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001 chr19 43.4:43.6 RYR1,SIPA1L3,DPF1,PPP1R14A,SPINT2,LOC541469,C19orf33,YIF1B,KCNK6,C19orf15,PSMD8,GGN,SPRED3,RASGRP4,FAM98C chr9 11.8:12 chr11 109.8:110.2 FDX1,ARHGAP20 chr14 97.6:97.8 chr13 87.8:88 chr10 20.4:20.6 PLXDC2 chr11 9.8:10.2 SBF2 chr9 99.6:99.8 ANP32B,C9orf156,FOXE1,HEMGN chr16 22.8:23 HS3ST2,USP31 chr4 119.8:120 KIAA1627,SEC24D,SYNPO2 chr4 119.2:119.6 NDST3,PRSS12 chr5 109:109.2 MAN2A1 chr3 4.4:4.6 SUMF1,ITPR1 chr1 200.8:201 PPP1R12B,SYT2,JARID1B chr19 56.6:56.8 ETFB,CLDND2,NKG7,LIM2,SIGLEC12,SIGLEC6,ZNF175,SIGLEC5,SIGLEC10,SIGLEC8,LOC729767 chr2 155.4:155.6 KCNJ3 chr8 49.2:49.4 chr8 140.2:140.4 chr20 46.6:47 PREX1,ARFGEF2 chr3 165.4:165.6 chr12 78:78.2 SYT1 chr22 34.2:34.4 MCM5,RASD2,MB,LOC284912,APOL6,APOL5 chr6 100.8:101 SIM1 chr3 165:165.2 chr9 114:114.2 SUSD1,ROD1,HSDL2 chr16 80:80.2 GAN,CMIP chr2 12.2:12.4 chr12 81.4:81.6 C12orf26,TMTC2 chr17 3.4:3.6 TRPV1,CTNS,TRPV3,CARKL,TAX1BP3,TMEM93,P2RX5,ITGAE,GSG2 chr7 20.4:20.6 ITGB8 chr13 29.4:29.6 LOC440131 chr12 28:28.2 PTHLH chr4 163:163.2 FSTL5 chr11 112.4:112.6 NCAM1 chr7 156.2:156.4 RNF32,LMBR1,NOM1 chr9 28.6:28.8 LINGO2 chr18 40.8:41.2 SETBP1 chr14 31.2:31.4 NUBPL chr9 138.8:139 MAMDC4,LCN10,LCN6,LCN8,UNQ2541,TMEM141,C9orf86,PHPT1,EDF1,TRAF2,FBXW5,C8G,PTGDS,FLJ45224,C9orf142,CLIC3,ABCA2,C9orf139,FUT7,KIAA1984,LCN12,LOC389813 chr8 21.2:21.4 chr11 6:6.2 OR52L1,OR56A1,OR56B4,OR52B2,OR52W1,C11orf42,C11orf56,CNGA4,CCKBR,OR56A4 chr8 113.8:114 CSMD3 chr9 94.6:94.8 ANKRD19,BICD2,ZNF484,FGD3 chrX 137.8:138 chr6 130.6:130.8 SAMD3,KIAA1913 chr3 100.8:101 COL8A1,FLJ44076,C3orf26,FILIP1L chr4 139:139.2 chr9 24:24.2 chr18 42.2:42.4 RNF165,LOXHD1 chr6 72.8:73 RIMS1 chr9 110.8:111 EPB41L4B,C9orf4,C9orf5,CTNNAL1 chr13 57:57.2 PCDH17 chr13 56.4:56.6 FLJ40296 0.05 chr9 114.6:114.8 TSCOT,ZFP37 chr3 56.6:56.8 CCDC66,C3orf63,ARHGEF3 chr18 64.8:65 CCDC102B chr11 83.8:84 DLG2 chr22 34.8:35 APOL3,APOL4,APOL2,APOL1,MYH9 chr4 34.2:34.4 chr6 77:77.2 chr11 87.4:87.6 RAB38 chr3 118.4:118.6 chr5 66.8:67.2 chr3 46:46.2 FYCO1,CXCR6,XCR1,CCR1 chr12 80.6:80.8 PPFIA2 chr16 25.8:26 HS3ST4 chr11 40.4:40.6 chr3 61:61.2 FHIT chr6 26.4:26.6 HIST1H4G,HIST1H3F,HIST1H2BH,HIST1H3G,HIST1H2BI,HIST1H4H,BTN3A2,BTN2A2,BTN3A1,BTN2A3,BTN3A3,BTN2A1,BTN1A1,HMGN4 chr1 79.6:79.8 chr5 43:43.2 AXIIR,ZNF131,MGC42105 chr21 29.4:29.6 CCT8,C21orf7,BACH1 chr6 29.6:29.8 MAS1L,OR2H2,GABBR1,MOG,HLA−F chr2 98.2:98.4 INPP4A,MGC26733,CNGA3 chr7 92:92.2 MGC40405,CDK6,DKFZP564O0523,PEX1 chr15 54.2:54.4 RFXDC2,TEX9 chr1 79:79.2 chr7 82.6:82.8 SEMA3E chr7 141:141.2 AGK,FLJ40852,SSBP1,TAS2R3,TAS2R4,TAS2R5,LOC136242,KIAA1147 chr14 71.8:72 RGS6 chr1 173.4:173.6 TNN,KIAA0040,TNR chr8 5.2:5.4 chr4 130.2:130.4 SCLT1,C4orf33 chr3 76.8:77 chr1 88.8:89 PKN2 chr5 162:162.2 chr9 76:76.2 chr8 9.2:9.4 chr21 43:43.2 PDE9A,WDR4,NDUFV3 chrX 125:125.2 WDR40C chr10 90.2:90.4 C10orf59,LIPL1,LIPF chr8 68.8:69 CPA6,DEPDC2 chr6 70.6:70.8 LMBRD1,COL19A1 chr9 81:81.2 chr6 75.4:75.6 chr5 145.8:146 TCERG1,GPR151,PPP2R2B chr5 163.4:163.6 chr17 42.6:42.8 CDC27,MYL4,ITGB3,C17orf57 chr15 59.8:60 VPS13C chr21 44.8:45 C21orf29,KRTAP10−1,KRTAP10−2,KRTAP10−3,KRTAP10−4,KRTAP10−5,KRTAP10−6,KRTAP10−7,KRTAP10−8,KRTAP10−9,KRTAP10−10,KRTAP10−11,KRTAP12−4,KRTAP12−3,KRTAP12−2,KRTAP12−1,KRTAP10−12,UBE2G2,SUMO3 chr10 58:58.2 chr12 5.2:5.4 chr2 86.6:86.8 JMJD1A,VPS24,RNF103,RMND5A chr10 68.8:69 CTNNA3 chr15 74.4:74.6 ISL2,ZNF291,ETFA

Figure 13: The top 1% of iHS signals in the Bantu, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 16 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001 chr9 31.2:31.6 chr7 66.6:67 chr2 97.6:97.8 COX5B,ACTR1B,ZAP70,KIAA1641 chr5 109:109.2 MAN2A1 chr6 26.4:26.6 HIST1H4G,HIST1H3F,HIST1H2BH,HIST1H3G,HIST1H2BI,HIST1H4H,BTN3A2,BTN2A2,BTN3A1,BTN2A3,BTN3A3,BTN2A1,BTN1A1,HMGN4 chr3 29.4:29.8 RBMS3 chr11 57.8:58 OR10Q1,OR10W1,OR5B17,OR5B3,OR5B2,OR5B12,OR5B21 chr3 133.2:133.4 CPNE4 chr6 85.4:85.6 TBX18 chr13 35.4:35.6 DCAMKL1,SOHLH2 chr2 99.6:99.8 AFF3 chr9 86:86.2 SLC28A3 chr9 75.2:75.4 chr15 53.8:54 PRTG,NEDD4 chr3 75:75.2 chr15 54.8:55 SUHW4,TCF12 chr9 13.6:13.8 chr12 70.6:70.8 TBC1D15,TPH2 chr15 55.2:55.4 TCF12 chr2 55:55.2 RTN4,FLJ42562 chr4 160.8:161.2 chr5 130:130.2 chr3 155.2:155.4 SGEF chr1 5:5.2 chr16 11:11.2 KIAA0350 chr2 173:173.2 ITGA6,PDK1 chr7 28.6:28.8 CREB5 chr19 36.6:36.8 chr10 19:19.2 NSUN6,ARL5B chr3 27.2:27.4 NEK10,SLC4A7 chr7 29.8:30 SCRN1,FKBP14,PLEKHA8,WIPF3 chr7 40.6:40.8 C7orf10 chr5 123:123.2 CSNK1G3 chr18 40.8:41 SETBP1 chr20 57.6:57.8 PHACTR3 chr2 43.6:43.8 THADA,PLEKHH2 chr10 67.4:67.6 CTNNA3 chr2 84.6:84.8 FLJ37357 chr7 84.2:84.4 chr11 16.4:16.6 SOX6 chr11 76.6:76.8 GDPD4,PAK1,MYO7A chr18 19.2:19.4 RIOK3,C18orf8,NPC1,ANKRD29,C18orf45 chr3 20:20.2 C3orf48,EFHB,RAB5A,PCAF,SGOL1 chr10 3:3.2 PFKP,PITRM1 chr1 189.8:190 chr13 57.4:57.6 chr5 14.2:14.4 TRIO chr7 9.4:9.6 chr5 26.6:26.8 chr2 42.2:42.4 EML4,COX7A2L chr2 229.8:230 DNER,PID1 0.05 chr5 136.2:136.4 SPOCK1 chr2 46.4:46.6 EPAS1,ATP6V1E2,RHOQ chr2 84.2:84.4 LOC388965 chr2 98.2:98.4 INPP4A,MGC26733,CNGA3 chr6 23.8:24 chr6 115.8:116 chr6 154.2:154.4 OPRM1 chr7 125.4:125.6 chr11 73.6:73.8 DKFZP586P0123,PPME1,P4HA3,PGM2L1,KCNE3 chr15 42.8:43 B2M,TRIM69,C15orf43 chr2 50.2:50.4 NRXN1 chr15 51.2:51.4 chr6 159.8:160.2 SOD2,WTAP,ACAT2,TCP1,MRPL18,PNLDC1,MAS1 chr6 19:19.2 chr7 2.8:3 GNA12,CARD11 chr15 97.4:97.6 TTC23,LRRC28,DMN chr2 209.8:210 MAP2 chr5 140.8:141 PCDHGA1,PCDHGA2,PCDHGA3,PCDHGB1,PCDHGA4,PCDHGB2,PCDHGA5,PCDHGB3,PCDHGA6,PCDHGA7,PCDHGB4,PCDHGA8,PCDHGB5,PCDHGA9,PCDHGB6,PCDHGA10,PCDHGB7,PCDHGA11,PCDHGA12,PCDHGC3,PCDHGC4,PCDHGC5,HDAC3,C5orf16,FCHSD1,CENTD3,DIAPH1 chr15 63.2:63.4 PDCD7,CLPX,CILP,PARP16,PUNC chr3 76.8:77 chr3 3.6:3.8 LRRN1 chr5 108.4:108.6 FER chr6 131.2:131.4 EPB41L2 chr5 18.2:18.4 chr13 90.4:90.6 chr3 63:63.2 chr20 37.8:38 chr5 135.4:135.6 TGFBI,SMAD5,TRPC7 chr14 64.8:65 FUT8 chr14 80.4:80.6 C14orf145,TSHR chr9 114.6:114.8 TSCOT,ZFP37 chrX 145.6:145.8 chr2 25.2:25.4 POMC,DNMT3A chr22 31.6:31.8 SYN3,TIMP3 chr8 69.6:69.8 C8orf34 chr1 5.8:6 NPHP4,KCNAB2 chr11 38.4:38.6 chr11 104.6:104.8 chr1 79:79.2 chr21 40.8:41 DSCAM chr9 110.8:111 EPB41L4B,C9orf4,C9orf5,CTNNAL1 chr4 130.2:130.4 SCLT1,C4orf33 chr5 160.2:160.4 chr16 78.6:78.8 chr5 129.2:129.4 CSS3 chr6 56:56.2 COL21A1 chr18 60.2:60.4 chr6 2.2:2.4 GMDS chr6 133:133.2 TAAR2,TAAR5,TAAR1,VNN1,VNN3,VNN2,C6orf192,RPS12 chr10 119.4:119.6

Figure 14: The top 1% of iHS signals in the Biaka Pygmies, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 17 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001

chr2 167.6:168 CMYA3 chr17 60.6:60.8 RGS9 chr9 107:107.2 SLC44A1 chr14 60.8:61.2 TMEM30B,PRKCH,HIF1A chr5 112.4:112.6 DCP2,MCC chr4 60.6:61 chr9 3.2:3.4 RFX3 chr3 131.4:131.8 FLJ35880 chr3 25.8:26 NGLY1,OXSM chr2 178:178.2 PDE11A,AGPS,TTC30A,TTC30B chr8 52.6:53 PCMTD1 chr8 139.6:139.8 C8ORFK32,COL22A1 chr7 119.8:120.2 KCND2,TSPAN12 chr6 30:30.4 HLA−A,HCG9,ZNRD1,RNF39,TRIM31,TRIM40,TRIM15,TRIM26,FLJ45422,TRIM39,RPP21,PPP1R11 chr18 19.6:19.8 LAMA3,C18orf17 chr2 197.4:197.6 GTF3C3,UNQ6411,PGAP1,ANKRD44 chr5 145.8:146.2 TCERG1,GPR151,PPP2R2B chr8 140:140.2 COL22A1 chr15 91.8:92 chr5 21.8:22 CDH12 chr2 158.2:158.6 ACVR1C,ACVR1,UPP2 chr2 195.4:195.6 chr15 67.2:67.4 GLCE,PAQR5 chr6 105.8:106 PREP chr9 12.4:12.8 TYRP1,C9orf150 chr4 34:34.2 chr10 83.6:83.8 NRG3 chr5 74.6:74.8 HMGCR,COL4A3BP,POLK chr16 80.8:81 MPHOSPH6 chr4 186.4:186.6 SNX25,LRP2BP,ANKRD37,C4orf20,CCDC110 chr14 62.8:63 RHOJ,GPHB5,PPP2R5E chr9 125.4:125.6 DENND1A chr5 142:142.4 FGF1,ARHGAP26 chr12 40:40.2 PDZRN4 chr7 36.8:37.2 ELMO1 chr4 148.4:148.6 EDNRA chr1 65.2:65.4 AK3L1,AK3L2,JAK1 chr18 7.4:7.6 PTPRM chr1 160.2:160.6 ATF6,OLFML2B,NOS1AP,C1orf111,SH2D1B chr21 29.8:30 GRIK1 chr4 32.6:32.8 chr12 101:101.2 CCDC53,NUP37,PMCH,C12orf48 chr2 238:238.2 COL6A3,PRLH,RAB17,MLPH chr10 84:84.2 NRG3 chr12 110.2:110.4 FAM109A,SH2B3,ATXN2,CUTL2 chr1 244:244.2 SMYD3 chr5 23.2:23.4 0.05 chr18 24.8:25 chr6 24.2:24.4 NRSN1,DCDC2 chr8 30:30.2 TMEM66,LEPROTL1,DCTN6 chr9 86.4:86.6 NTRK2 chr10 115:115.2 chr7 19.2:19.4 FERD3L chr4 29.8:30 chr17 51.2:51.4 TMEM100,PCTP chr16 78.2:78.6 MAF chr9 93.2:93.4 AUH,NFIL3 chr2 40.2:40.4 SLC8A1 chr15 85.2:85.4 AGBL1 chr1 11.4:11.6 FBXO2,FBXO44,FBXO6 chr9 110.8:111 EPB41L4B,C9orf4,C9orf5,CTNNAL1 chr15 27:27.2 APBA2 chr11 20.8:21 NELL1 chr2 123:123.2 chr5 24.6:24.8 CDH10 chr14 63.4:63.6 SYNE2 chrX 24:24.2 KLHL15,EIF2S3,ZFX chrX 93.2:93.4 chr6 30.6:30.8 IER3,PRR3,HLA−E,GNL1,ABCF1,PPP1R10,MRPS18B,C6orf134,C6orf136,DHX16,NRM,MDC1,TUBB,FLOT1 chr4 41.2:41.6 DKFZP686A01247,PHOX2B,TMEM33 chr3 72.6:72.8 RYBP chr3 100.6:100.8 COL8A1 chr13 18.6:18.8 TUBA3C chr4 14.2:14.4 chr5 38:38.2 chr12 61:61.2 USP15,MON2 chr17 9.4:9.6 WDR16,STX8,USP43 chr9 130:130.2 LCN2,CIZ1,DNM1,GOLGA2,TRUB2,COQ4,SLC27A4,URM1,CEECAM1,C9orf16 chr12 11.4:11.6 PRB4,PRB1,PRB2 chr11 87.2:87.4 chr12 123.2:123.4 NCOR2,FAM101A chr7 7.2:7.4 C1GALT1,COL28A1 chr16 76.8:77 WWOX chr2 147.4:147.6 chr8 52:52.2 chr16 1.6:1.8 MAPK8IP3,IFT140,CRAMP1L,HN1L,NME3,MRPS34,EME2,SPSB3,NUBP2,IGFALS,FAHD1,C16orf73,HAGH chr22 30.2:30.4 DRG1,EIF4ENIF1,SFI1,PISD,C22orf30 chr6 102.2:102.4 GRIK2 chr6 167.2:167.4 RPS6KA2,RNASET2,FGFR1OP chr5 115.6:115.8 COMMD10,SEMA6A chr3 103.6:103.8 ZPLD1 chr17 74.4:74.6 TIMP2,LGALS3BP,CANT1,C1QTNF1,FLJ21865 chr2 196.6:196.8 DNAH7,STK17B,HECW2

Figure 15: The top 1% of iHS signals in the Europeans, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 18 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001 chr9 107:107.2 SLC44A1 chr2 212.8:213.2 ERBB4 chr4 34:34.2 chr14 62.6:63 KCNH5,RHOJ,GPHB5,PPP2R5E chr5 19.6:20 CDH18 chr8 139.6:139.8 C8ORFK32,COL22A1 chr17 60.6:60.8 RGS9 chr15 27:27.2 APBA2 chr7 119.8:120.2 KCND2,TSPAN12 chr3 25.8:26 NGLY1,OXSM chr18 64.8:65 CCDC102B chr10 84:84.4 NRG3 chr20 21.2:21.4 C20orf19,XRN2,NKX2−2 chr12 40:40.4 PDZRN4 chr9 125.2:125.6 CRB2,DENND1A chr14 61:61.2 PRKCH,HIF1A chr21 29.6:30 BACH1,GRIK1 chr22 45:45.2 FLJ20699,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1 chr1 244:244.2 SMYD3 chr1 65:65.2 RAVER2,JAK1 chr2 238:238.2 COL6A3,PRLH,RAB17,MLPH chr8 116.8:117 TRPS1 chr8 140:140.2 COL22A1 chr12 124.6:124.8 TMEM132B chr5 145.8:146 TCERG1,GPR151,PPP2R2B chr5 30.6:30.8 chr11 129.4:129.6 PRDM10,C11orf37,APLP2,ST14,ZBTB44 chr6 108:108.2 SCML4,FLJ10159 chr2 158.2:158.6 ACVR1C,ACVR1,UPP2 chr4 60.6:61 chr5 142:142.4 FGF1,ARHGAP26 chr10 22.4:22.6 COMMD3 chr3 131.6:131.8 FLJ35880 chr5 110.2:110.4 TSLP chr3 113:113.2 TMPRSS7,PLCXD2,PHLDB2,ABHD10,TAGLN3 chr12 125.6:125.8 chr2 72.2:72.4 CYP26B1 chr7 33.6:33.8 BBS9 chr15 67.4:67.6 GLCE,PAQR5,KIF23,RPLP1,LOC729416 chr16 1.6:1.8 MAPK8IP3,IFT140,CRAMP1L,HN1L,NME3,MRPS34,EME2,SPSB3,NUBP2,IGFALS,FAHD1,C16orf73,HAGH chr16 77:77.2 WWOX chr12 98.2:98.4 ANKS1B chr12 10:10.4 FLJ46363,CLEC12A,CLEC1B,CLEC12B,CLEC9A,CLEC1A,CLEC7A,GABARAPL1,KLRD1,KLRK1,C12orf59,OLR1 chr2 195.4:195.6 chrX 19:19.2 GPR64 chr22 48.6:48.8 MLC1,BRD1,ZBED4,ALG12,CRELD2,PIM3,FLJ41993,LOC164714 chr20 22.2:22.6 FOXA2 chr17 59.6:59.8 ERN1,TEX2,PECAM1 chr3 64.2:64.4 PRICKLE2 0.05 chr14 63.4:63.6 SYNE2 chr12 87.2:87.4 KITLG chr20 48.8:49 PARD6B,BCAS4,ADNP,DPM1,MOCS3 chr8 52.8:53 PCMTD1 chr4 170.2:170.6 CBR4,SH3RF1,NEK1 chr11 83.4:83.6 DLG2 chr13 73.8:74 chr4 29.8:30 chr14 23.8:24 C14orf124,TGM1,CHMP4A,MDP−1,NEDD8,GMPR2,TINF2,RABGGTA,DHRS1,C14orf21,LTB4R2,LTB4R,ADCY4,NFATC4,KIAA0323,CMA1,RIPK3,CIDEB,CBLN3 chr2 1.8:2 MYT1L chr17 51:51.2 TMEM100,PCTP chr1 212.4:212.6 SMYD2,PTPN14 chr10 83.6:83.8 NRG3 chr15 91.8:92 chr1 246.2:246.4 OR2T8,OR2L13,OR2L8,OR2AK2,OR2L2,OR2L3,OR2M5,OR2M2,OR2M3 chr2 21.6:21.8 chr8 116:116.2 chr13 103:103.2 chr5 21.8:22 CDH12 chr4 148.4:148.6 EDNRA chr7 124.2:124.4 POT1,GPR37,LOC401398 chr8 55.2:55.4 LYPLA1,MRPL15 chr20 52.6:52.8 DOK5 chr11 17.6:17.8 MYOD1,SERGEF,KCNC1 chr4 43:43.2 chr5 92.4:92.6 chr2 152.2:152.4 NEB,ARL5A,CACNB4 chr5 24.6:24.8 CDH10 chr6 30:30.4 HLA−A,HCG9,ZNRD1,RNF39,TRIM31,TRIM40,TRIM15,TRIM26,FLJ45422,TRIM39,RPP21,PPP1R11 chr12 110.2:110.4 FAM109A,SH2B3,ATXN2,CUTL2 chr4 14.2:14.4 chr17 72.2:72.4 ST6GALNAC1,MXRA7,SFRS2,MFSD11,MGAT5B,PTDSR,LOC124512 chr4 5.2:5.4 STK32B chr5 115.6:115.8 COMMD10,SEMA6A chr20 54:54.2 CBLN4 chr12 65.8:66 CAND1 chrX 33.8:34 chr6 54.8:55 FAM83B chr3 88:88.2 HTR1F,CGGBP1 chr8 84.6:84.8 chr7 125.8:126 GRM8 chr4 130:130.2 PHF17,SCLT1,C4orf33 chr5 112.4:112.6 DCP2,MCC chr15 64.8:65 SMAD6 chr18 7.4:7.6 PTPRM chr5 74.6:74.8 HMGCR,COL4A3BP,POLK chr8 42.6:42.8 CHRNA6,THAP1,RNF170,CHRNB3 chr15 46:46.2 SLC24A5,MYEF2

Figure 16: The top 1% of iHS signals in the Middle East, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 19 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001

chr15 46:46.4 SLC24A5,MYEF2,SLC12A1,DUT chr17 51:51.4 TMEM100,PCTP chr7 119.8:120.2 KCND2,TSPAN12 chr14 62.6:63 KCNH5,RHOJ,GPHB5,PPP2R5E chr8 11:11.2 C8orf15,MTMR9,AMAC1L2,XKR6 chr22 45:45.2 FLJ20699,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1 chr10 83.8:84.2 NRG3 chr3 25.8:26 NGLY1,OXSM chr6 73.8:74 C6orf148,KCNQ5 chr8 139.6:139.8 C8ORFK32,COL22A1 chr9 125.2:125.6 CRB2,DENND1A chr6 30.2:30.6 PRR3,RNF39,TRIM31,TRIM40,TRIM15,TRIM26,FLJ45422,TRIM39,RPP21,HLA−E,GNL1,ABCF1 chr9 122.6:123 FBXW2,PSMD5,PHF19,TRAF1,C5,CEP110,RAB14 chr3 131.6:131.8 FLJ35880 chr2 237.2:237.4 CXCR7 chr1 234.8:235 LGALS8,HEATR1,ACTN2,MTR chr9 107:107.2 SLC44A1 chr21 29:29.2 N6AMT1,ZNF294 chr4 34:34.4 chr20 15.6:15.8 C20orf133 chr2 158.2:158.6 ACVR1C,ACVR1,UPP2 chr2 231.4:231.6 GPR55,CAB39,ITM2C,PSMD1 chr9 130:130.2 LCN2,CIZ1,DNM1,GOLGA2,TRUB2,COQ4,SLC27A4,URM1,CEECAM1,C9orf16 chr6 105.6:106 LIN28B,BVES,POPDC3,PREP chr4 29.6:30 chr5 117.4:117.6 chr15 27:27.2 APBA2 chr5 145.8:146 TCERG1,GPR151,PPP2R2B chr17 60.6:60.8 RGS9 chr3 142.2:142.4 SLC25A36,SPSB4,ACPL2 chr4 41.4:41.6 DKFZP686A01247,PHOX2B,TMEM33 chr18 64.8:65 CCDC102B chr5 112.4:112.6 DCP2,MCC chr2 218.8:219 GPBAR1,PNKD,ARPC2,TMBIM1,MGC50811,SLC11A1,CTDSP1,VIL1,USP37,AAMP chr12 81.8:82 TMTC2 chr8 21.8:22 NUDT18,DOK2,XPO7,NPM2,FGF17,EPB49,RAI16,HR chr21 16.2:16.4 USP25,C21orf34 chr7 86.4:86.6 KIAA1324L,DMTF1 chr3 25.4:25.6 RARB,TOP2B chr16 78.4:78.6 chr2 223.4:223.8 ACSL3,KCNE4 chr12 98.2:98.4 ANKS1B chrX 66.4:66.6 chr14 64.2:64.6 PLEKHG3,SPTB,CHURC1,GPX2,RAB15,FNTB,MAX chr2 178:178.2 PDE11A,AGPS,TTC30A,TTC30B 0.05 chr5 25:25.2 chr9 86.4:86.6 NTRK2 chr13 67:67.2 chr8 52.6:53 PCMTD1 chr3 66.8:67 chr8 92:92.2 EFCBP1,TMEM55A,OTUD6B chr11 129.4:129.6 PRDM10,C11orf37,APLP2,ST14,ZBTB44 chr9 93.6:93.8 ROR2,SPTLC1 chr20 48.8:49 PARD6B,BCAS4,ADNP,DPM1,MOCS3 chr8 10.6:10.8 RP1L1,C8orf74,SOX7,PINX1,XKR6 chr8 42.6:42.8 CHRNA6,THAP1,RNF170,CHRNB3 chr10 59.4:59.8 IPMK,ZCD1,UBE2D1,TFAM chr21 29.4:29.8 CCT8,C21orf7,BACH1,GRIK1 chr7 37:37.2 ELMO1 chr11 113.4:113.6 HTR3A,ZBTB16 chr22 33.6:33.8 ISX chr5 38:38.2 chr12 79.2:79.4 C12orf64 chr4 180.2:180.4 chr13 103:103.2 chr4 173.8:174 GALNT17 chr4 170.2:170.4 CBR4,SH3RF1 chr14 63.4:63.6 SYNE2 chr15 64.8:65 SMAD6 chr13 74:74.2 chr9 32.6:32.8 NDUFB6,TAF1L,LOC401498 chr2 196.6:196.8 DNAH7,STK17B,HECW2 chr20 9.4:9.6 PLCB4,C20orf103,PAK7 chr12 18.8:19 PLCZ1,CAPZA3 chr8 140:140.2 COL22A1 chr20 22.4:22.6 FOXA2 chr8 98.4:98.6 TSPYL5 chr12 92.4:92.6 UBE2N,MRPL42,SOCS2,CRADD chr6 29.2:29.4 OR2B3,OR5U1,OR5V1,OR12D3,LOC651503 chr7 148.4:148.6 ZNF783,PDIA4,ZNF786,ZNF425,ZNF398,ZNF212,ZNF282 chr12 87.2:87.4 KITLG chr16 82.4:82.6 CDH13,HSBP1,EFCBP2,MBTPS1,OSGIN1,MLYCD,LOC146167 chr6 83.4:83.6 chr22 24.2:24.4 ADRBK2 chr7 118.2:118.4 chrX 121.2:121.4 chr3 176.6:176.8 NAALADL2 chr11 87.2:87.4 chr5 121:121.2 FTMT chr13 59:59.2 DIAPH3

Figure 17: The top 1% of iHS signals in South Asia, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 20 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001

chr2 108.8:109 RANBP2,FLJ32745,EDAR chr2 212.6:213 ERBB4 chr6 125.8:126.2 HEY2,NCOA7 chr2 108:108.4 SLC5A7,SULT1C3,SULT1C1,SULT1C2,GCC2 chr10 55.6:55.8 PCDH15 chr10 94.8:95.2 EXOC6,CYP26C1,CYP26A1,FER1L3,CEP55 chr5 112.2:112.6 APC,SRP19,DCP2,MCC,REEP5 chr10 55:55.2 chr11 25.2:25.6 chr12 1.2:1.4 ERC1 chr13 103.8:104 chr2 125.8:126.2 chr17 45.8:46.2 MRPL27,EME1,LRRC59,FLJ20920,CHAD,RSAD1,EPN3,SPATA20,CACNA1G,ABCC3,ANKRD40,CROP,XYLT2,MYCBPAP chr4 170.2:170.6 CBR4,SH3RF1,NEK1 chr9 110.2:110.6 chr13 62.6:62.8 chr8 32:32.2 NRG1 chr22 38.2:38.4 MAP3K7IP1,MGAT3,SMCR7L,ATF4,RPS19BP1,CACNA1I chr2 17:17.4 chr1 73.6:73.8 chr5 108:108.2 FER chr5 25:25.2 chr10 52.8:53 PRKG1 chr10 94.4:94.6 KIF11,HHEX,EXOC6 chr20 58.2:58.4 LOC284757 chr9 125.2:125.6 CRB2,DENND1A chr16 17.2:17.4 XYLT1 chr7 86.2:86.4 GRM3,KIAA1324L chr2 172.8:173.2 ITGA6,PDK1 chr16 64.2:64.4 chr2 38.2:38.4 CYP1B1,MGC34824,ARL6IP2 chr1 65.8:66 LEPR,PDE4B chr4 105.2:105.6 CXXC4 chr15 62:62.2 DAPK2,FAM96A,SNX1,SNX22,PPIB,CSNK1G1 chr7 3.8:4.2 SDK1 chr10 11:11.2 CUGBP2 chr16 76:76.2 ADAMTS18 chr1 75.6:76 SLC44A5,ACADM,RABGGTB,MSH4 chr4 158.6:159 chr9 110.8:111 EPB41L4B,C9orf4,C9orf5,CTNNAL1 chr1 103.2:103.4 COL11A1 0.05 chr4 28.2:28.6 chr6 159:159.2 DYNLT1,VIL2,LOC202459,SYTL3 chr3 71.4:71.6 FOXP1 chr2 29.2:29.4 FLJ34931,CLIP4,ALK chr10 4.2:4.4 chr22 34.8:35.2 APOL3,APOL4,APOL2,APOL1,MYH9,TXN2,FOXRED2,EIF3S7 chr4 144.4:144.6 USP38,GAB1 chr13 110.6:110.8 ARHGEF7,C13orf16 chrX 86.2:86.4 chr3 62.6:62.8 CADPS chr10 15.4:15.6 C10orf38,ITGA8 chr7 126.6:127 GRM8,ZNF800,GCC1,ARF5,FSCN3,PAX4 chr3 176.6:177 NAALADL2 chr7 111.8:112 ZNF277P,IFRD1,FLJ39575 chr3 27.2:27.4 NEK10,SLC4A7 chr5 139:139.2 UBE2D2,CXXC5,PSD2,NRG2 chr7 50:50.2 ZPBP chr11 81:81.2 chr3 169:169.2 SERPINI1,GOLPH4 chr9 15.8:16 C9orf93 chr4 160.4:160.8 chr1 232.8:233 IRF2BP2 chr1 74.6:74.8 TNNI3K,C1orf173 chr18 29.4:29.6 chr2 178.4:178.6 PDE11A chr16 78.4:78.6 chr13 62:62.2 chr6 32.2:32.4 C6orf10,TNXB,CREBL1,FKBPL,PRRT1,PPT2,EGFL8,AGPAT1,RNF5,AGER,GPSM3,NOTCH4,LOC401252,PBX2 chr1 171.2:171.4 TNFSF18,TNFSF4 chr5 172.8:173 FAM44B chr4 153:153.2 chr6 105.6:105.8 LIN28B,BVES,POPDC3,PREP chr7 138.2:138.4 ZC3HAV1L,ZC3HAV1 chr3 197.4:197.6 TM4SF19,FLJ25996,ZDHHC19,OSTalpha,PCYT1A,MGC33212 chr8 11:11.2 C8orf15,MTMR9,AMAC1L2,XKR6 chr9 23:23.2 chr10 73.6:73.8 ASCC1,C10orf104,DDIT4,DNAJB12,CBARA1 chr3 114.4:114.6 BOC,WDR52,CCDC52 chr2 43.6:43.8 THADA,PLEKHH2 chr5 38:38.2 chr2 56.6:56.8

Figure 18: The top 1% of iHS signals in East Asia, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 21 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001

chr16 11:11.4 PRM1,KIAA0350,SOCS1,TNP2,PRM3,PRM2,C16orf75,LOC400499 chr2 161.2:161.6 chr6 47.6:47.8 GPR115,GPR111,CD2AP chr10 110:110.2 chr12 30.8:31 C1QDC1,TSPAN11 chr6 122.6:122.8 HSF2,SERINC1,PKIB chr13 87.8:88.2 chr5 141:141.2 HDAC3,C5orf16,FCHSD1,CENTD3,PCDH1,DIAPH1 chr4 68.6:68.8 TMPRSS11F,CHR415SYT,TMPRSS11B chr8 33.4:33.6 FUT10,RBM13,C8orf41,RNF122,DUSP26 chr16 8.4:8.6 C16orf68 chr20 52:52.2 BCAS1,CYP24A1 chr3 158:158.2 FLJ16641 chr7 107.8:108 NRCAM,PNPLA8,THAP5,DNAJB9 chr1 159.8:160.2 FCGR2A,HSPA6,FCGR3A,FCGR2C,FCGR3B,FCGR2B,FCRLA,FCRLB,DUSP12,ATF6,OLFML2B chr21 39.6:39.8 C21orf87,BRWD1,HMGN1,WRB,C21orf13,SH3BGR,LOC728776 chr6 123:123.2 PKIB,FABP7,SMPDL3A chr7 100.4:100.6 MUC17,TRIM56,SERPINE1,AP1S1,VGF,FLJ39237,MOGAT3,PLOD3,ZNHIT1 chr6 73:73.2 RIMS1 chr8 95.6:95.8 RAD54B,KIAA1429,RBM35A,DPY19L4 chr3 21.2:21.4 ZNF659 chr6 54.6:55 FAM83B chr12 30.2:30.4 chr12 3.6:3.8 PRMT8,EFCAB4B,PARP11 chr3 24.8:25 chr1 196.4:196.6 NEK7 chr5 80.8:81.2 SSBP2 chr21 40:40.2 B3GALT5,PCP4,LOC150084 chr5 153.6:153.8 GALNT10,SAP30L,HAND1 chr6 122.2:122.4 chr11 69:69.2 CCND1,FLJ42258,ORAOV1,FGF19 chr2 3.2:3.4 TSSC1,TTC15 chr17 32.4:32.6 LHX1,AATF,ACACA chr22 48.4:48.6 C22orf34,BRD1,ZBED4 chr2 54.8:55.2 SPTBN1,RTN4,FLJ42562 chr11 6.6:6.8 KIAA0409,ILK,TAF10,DCHS1,MRPL17,OR2AG2,OR2AG1,OR6A2,OR10A5,OR10A2,TPP1 chr12 73.6:73.8 KCNC2 chr7 131.6:131.8 PLXNA4B chr2 17.8:18 SMC6,FLJ40869,KCNS3 chr6 119.2:119.4 MCMDC1,ASF1A,C6orf60 chr12 107.8:108 SSH1,DAO,SVOP,USP30,ALKBH2,UNG chr2 36:36.2 chr4 143.8:144 0.05 chr14 100:100.2 WDR25,KIAA1446,C14orf70 chr5 107.2:107.4 FBXL17 chr11 56.6:56.8 LRRC55,AGTRL1,TNKS1BP1 chr12 26.2:26.6 BHLHB3,SSPN,ITPR2 chr2 160.8:161 ITGB6,RBMS1 chr12 46.2:46.4 FLJ21908,P11,RAPGEF3 chr2 7:7.2 RNF144,RSAD2 chr6 154.4:154.6 OPRM1,PIP3−E chr17 34.4:34.6 FBXO47,PLXDC1,CACNB1,RPL19,STAC2 chr18 32.6:32.8 FHOD3,C18orf10,KIAA1328 chr15 34:34.2 chr10 31.2:31.4 ZNF438 chr17 36.2:36.4 KRT28,KRT40,KRT25,KRT26,KRT27,KRT10,KRT12,KRT20,KRT23,KRT39,KRTAP3−3,KRTAP3−2,KRTAP3−1,KRTAP1−5,KRTAP1−3,TMEM99 chr2 26.4:26.6 GPR113,SELI,C2orf39,OTOF,HADHB chr2 52:52.2 chr1 197.2:197.4 chr5 164.6:164.8 chr5 154.8:155 chr3 24.2:24.4 THRB chrX 8.4:8.6 VCX−C,KAL1 chr2 169.4:169.6 NOSTRIN,SPBC25,G6PC2,ABCB11,DHRS9 chr6 47:47.2 GPR116,GPR110 chr15 56.2:56.4 AQP9 chr2 26.8:27 CENPA,KCNK3,DPYSL5,MAPRE3,C2orf18 chr4 60:60.2 chr6 119.6:119.8 MAN1A1 chr1 89.6:89.8 GBP6,LRRC8B chr4 164:164.2 chr12 7.6:7.8 APOBEC1,GDF3,DPPA3,CLEC4C,NANOG chr3 1.6:2 chr7 122.6:122.8 SLC13A1 chr20 2.8:3 PTPRA,FAM113A,VPS16,GNRH2,MRPS26,OXT,AVP,UBOX5 chr16 78.6:78.8 chr2 160.4:160.6 CD302,LY75,PLA2R1 chr15 50.8:51 KIAA1370,ONECUT1 chr6 35:35.2 C6orf107,TAF11,ANKS1A,TCP11 chr6 111.6:111.8 SLC16A10,KIAA1919,REV3L chr13 37.4:37.6 chr4 129.4:129.6 LARP2,PGRMC2 chr6 46.6:46.8 CYP39A1,TDRD6,PLA2G7,SLC25A27 chr15 56.8:57 ADAM10,SLTM,FAM63B chr1 164.8:165

Figure 19: The top 1% of iHS signals in the Americas, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 22 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001

chr8 63.8:64 FAM77D chr3 67.6:67.8 SUCLG2 chr2 165.2:165.6 GRB14,COBLL1,FLJ39822 chr2 126:126.2 chr14 69.4:69.6 SMOC1,SLC8A3 chr5 61.2:61.4 chr6 29.4:29.6 OR5U1,OR5V1,OR12D3,OR12D2,OR11A1,OR10C1,OR2H1,MAS1L chr3 162.6:162.8 C3orf57,LOC131149 chr12 92.8:93 CRADD chr2 165.8:166.2 SCN2A,SCN3A,FAM130A2 chr8 121.6:121.8 MTBP,SNTB1 chr9 1.6:1.8 chr2 3.2:3.6 TSSC1,TTC15,ADI1,RNASEH1,RPS7,COLEC11 chr5 63.8:64 RGS7BP,P18SRP chr20 5.8:6 C20orf196,CHGB,CGI−09,MCM8,CRLS1,C20orf75,C20orf42 chr1 183:183.2 EDEM3,FAM129A chr2 22.6:22.8 chr1 162.4:162.6 chr4 14.6:14.8 CPEB2 chr18 24.4:24.6 chr15 96.8:97 FLJ39743,IGF1R chr13 43.6:43.8 C13orf21 chr6 132.2:132.6 CTGF,ENPP1 chr15 51.6:51.8 WDR72 chr9 126.8:127 C9orf126,PPP6C,RABEPK,HSPA5 chr10 76.4:76.6 DUPD1,DUSP13,SAMD8,VDAC2,MYST4 chr13 110.4:110.6 ANKRD10,ARHGEF7 chr16 77.2:77.6 WWOX chr1 70.2:70.4 LRRC40,SFRS11,LRRC7 chr3 162.2:162.4 PPM1L,B3GALNT1,NMD3 chr8 14:14.2 SGCZ chr6 39.6:39.8 KIF6 chr13 46:46.2 LRCH1,ESD chr8 63.2:63.6 FAM77D chr4 113.4:113.6 C4orf16,TIFA,ALPK1 chr8 5.8:6 chr7 120.4:120.8 ING3,FLJ21986,WNT16,FAM3C chr6 160.2:160.4 IGF2R,PNLDC1,MAS1 chr2 178:178.2 PDE11A,AGPS,TTC30A,TTC30B chr17 61.2:61.4 CCDC46 chr14 68.4:68.6 ACTN1,WDR22 chr1 185.4:185.6 chr17 40.2:40.4 ADAM11,DBF4B,HIGD1B,EFTUD2,CCDC103,GFAP,C1QL1,GJA7,LOC146909 chr2 212.8:213 ERBB4 0.05 chr10 80:80.2 chr2 2.8:3 chr8 17.8:18 FGL1,PCM1,ASAH1 chr9 125:125.4 CRB2,STRBP,DENND1A chr6 108.8:109 LACE1,FOXO3A chr10 49.8:50 LRRC18,C10orf72 chr2 81.8:82 chr3 38.4:38.6 XYLB,ENDOGL1,ACVR2B,SCN5A chr2 212.4:212.6 ERBB4 chr5 64.4:64.6 SDCCAG10,ADAMTS6 chr3 26.6:26.8 LRRC3B chr16 50.8:51 TNRC9 chr13 101.6:101.8 FGF14 chr1 182.4:182.6 C1orf21 chr1 207:207.2 chr1 148.8:149 ECM1,ADAMTSL4,C1orf138,MCL1,ENSA,GOLPH3L,HORMAD1,CTSS,CTSK,ARNT chr2 151.6:151.8 RBM43,NMI chr4 60.6:60.8 chr7 124.8:125 chr10 44.8:45 RASSF4,C10orf10,C10orf25,ZNF22 chrX 12.4:12.6 FRMPD4 chr9 0.6:1 ANKRD15,DMRT1,DMRT3,DMRT2 chr22 41:41.2 NFAM1,SERHL,CGI−96 chr5 114.8:115 FEM1C,TICAM2,TMED7 chr20 40:40.2 PTPRT chr3 171.4:171.6 PHC3,PRKCI,SKIL,CLDN11 chr2 198.2:198.4 RFTN2,MARS2,BOLL chr7 103.6:103.8 LHFPL3,ORC5L chr7 19.2:19.4 FERD3L chr11 33.6:33.8 C11orf69,CD59,FBXO3,LMO2 chr5 169.6:169.8 LCP2,KCNIP1,KCNMB1 chr1 175.4:175.6 ASTN1,FAM5B chr22 41.6:41.8 ARFGAP3,PACSIN2,TTLL1,BIK chr2 213.6:213.8 IKZF2 chr10 43.4:43.6 ZNF239,ZNF485,ZNF32 chr6 56.2:56.4 COL21A1,DST chr12 41.8:42 ADAMTS20 chr12 119.4:119.6 COQ5,COX6A1,TRIAP1,15E1.2,SFRS9,DYNLL1,RNF10,POP5,CABP1,KIAA0152,ACADS,MGC5139 chr18 9.2:9.4 ANKRD12,TWSG1 chr20 17.2:17.4 PCSK2,BFSP1 chr10 76:76.2 ADK chr5 58.4:58.6 PDE4D chr7 23.8:24 STK31

Figure 20: The top 1% of iHS signals in Oceania, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 23 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001 chr13 24.2:24.4 ATP12A,CENPJ,RNF17 chr20 34.8:35 NDRG3,DSN1,C20orf117,C20orf118,SAMHD1 chr17 0.6:0.8 VPS53,FAM57A,C17orf25,RNMTL1,NXN,TIMM22,GEMIN4 chr6 164.6:164.8 chr19 47:47.2 CEACAM6,LYPD4,RPS19,ARHGEF1,RABAC1,ATP1A3,GRIK5,DMRTC2,CEACAM3,CD79A chr6 52:52.2 PKHD1,IL17A,IL17F,MCM3 chr3 121.8:122 NDUFB4,GTF2E1,HGD,RABL3 chr14 84.6:84.8 chr11 18.6:18.8 SPTY2D1,TMEM86A,IGSF22,PTPN5,UEVLD chr17 21.2:21.6 MAP2K3,KCNJ12 chr11 63:63.2 HRASLS5,LGALS12,RARRES3,HRASLS2,HRASLS3,DKFZP564J0863,RTN3 chr13 59.6:59.8 DIAPH3 chr1 207:207.2 chr2 59:59.2 chr3 194.2:194.4 HRASLS chr19 45.6:45.8 PLD3,HIPK4,SERTAD1,SERTAD3,BLVRB,SHKBP1,PRX,SPTBN4,LTBP4 chr12 106.2:106.4 BTBD11 chr18 44.8:45 DYM chr17 58.8:59 CYB561,ACE,KCNH6,CCDC44,WDR68 chr10 92:92.2 chr13 58.6:58.8 chr10 86:86.2 LRRC21,LRRC22,PCDH21,RGR,KIAA1128 chr10 42.8:43 RASGEF1A,RET,GALNACT−2 chr3 148.4:148.6 ZIC4,ZIC1 chr22 34:34.2 HMG2L1,TOM1,HMOX1,MCM5 chr10 12.4:12.6 CAMK1D chr1 115.6:115.8 NGFB chr21 43.6:43.8 SNF1LK,FLJ41733,C21orf125,HSF2BP chr12 54.6:54.8 IKZF4,WIBG,DGKA,SILV,CDK2,RAB5B,SUOX,RPS26,ERBB3,RPL41,ZC3H10,FAM62A,MYL6B,MYL6,SMARCC2,PA2G4 chr6 72.4:72.6 chr6 158.6:158.8 TULP4 chr2 105.2:105.4 GPR45,TGFBRAP1,C2orf49,FHL2 chr7 96.4:96.6 DLX6,DLX5,ACN9 chr3 185.4:185.6 DVL3,AP2M1,ABCF3,ALG3,MGC2408,ECE2,CAMK2N2,PSMD2,EIF4G1,C3orf40,CLCN2,POLR2H,THPO,CHRD chr14 90:90.2 TTC7B chr7 153.4:153.6 DPP6 chr16 86.4:86.6 KLHDC4,SLC7A5,CA5A,BANP chrX 41.4:41.8 CASK,GPR34,GPR82 chrX 33.2:33.4 DMD chr7 38.8:39 VPS41,POU6F2 chr20 16.4:16.6 C20orf23 chr8 106.4:106.6 ZFPM2 chr7 45.2:45.4 RAMP3 chr17 52.4:52.6 AKAP1,COIL,SCPEP1 chr11 43.4:43.6 TTC17 chr17 76:76.2 KIAA1303,RNF213,FLJ35220,NPTX1 chr8 4.8:5 CSMD1 chr19 48.4:48.6 PSG5,PSG4,PSG9,TEX101,CD177 chr5 60.8:61 FLJ37543 chr1 113.8:114.2 MAGI3,PHTF1,RSBN1,PTPN22,C1orf178,AP4B1,DCLRE1B chr7 36.4:36.6 KIAA0895,ANLN,AOAH chr1 39.2:39.4 RHBDL2,C1orf108,NDUFS5,MACF1 chr2 49.8:50 NRXN1 chr12 28:28.2 PTHLH chr7 106.4:106.8 PRKAR2B,HBP1,COG5 chr1 177.2:177.4 RALGPS2,FAM20B,ABL2,TOR3A chr8 26.6:26.8 ADRA1A,DPYSL2 chr2 50.8:51 NRXN1 chr8 59.6:59.8 CYP7A1,SDCBP,NSMAF chr3 45.6:45.8 LARS2,SACM1L,SLC6A20,LZTFL1,LIMD1 chr16 4.2:4.4 TFAP4,Magmas,CORO7,VASN,DNAJA3,GLIS2 chr9 134.8:135 C9orf9,TSC1,GFI1B,GTF3C5,CEL,RALGDS,GBGT1 0.05 chr17 3.4:3.6 TRPV1,CTNS,TRPV3,CARKL,TAX1BP3,TMEM93,P2RX5,ITGAE,GSG2 chr11 13.6:13.8 MLSTD2 chr19 0.6:0.8 HCN2,POLRMT,FGF22,FLJ45684,RNF126,PRSSL1,C19orf21,PTBP1,PRG2,AZU1,PRTN3,ELA2,CFD,THRAP5,C19orf22,FSTL3,PALM chr1 82.4:82.8 chr12 97.6:97.8 IKIP,APAF1,ANKS1B chr19 5.2:5.4 PTPRS,ZNRF4 chr11 132.4:132.6 OPCML chr10 15.8:16.2 ITGA8,C10orf97 chr7 62.2:62.4 chr18 40.8:41 SETBP1 chr6 26.4:26.6 HIST1H4G,HIST1H3F,HIST1H2BH,HIST1H3G,HIST1H2BI,HIST1H4H,BTN3A2,BTN2A2,BTN3A1,BTN2A3,BTN3A3,BTN2A1,BTN1A1,HMGN4 chr19 50.4:50.6 TRAPPC6A,EXOC3L2,MARK4,CKM,ERCC2,PPP1R13L,CD3EAP,ERCC1,BLOC1S3,KLC3 chr11 76.4:76.6 PHCA,CAPN5,OMP,GDPD4,B3GNT6,MYO7A chr9 25:25.2 chr14 100.2:100.4 C14orf70,DLK1 chr7 23:23.2 FAM126A,KLHL7,NUPL2 chr4 109.2:109.4 LEF1,HADH chrX 62.8:63 ARHGEF9 chr20 37.8:38 chrX 8:8.2 VCX2 chr4 180.4:180.6 chr4 147:147.2 LOC152485 chr2 213.6:213.8 IKZF2 chr22 26.4:26.6 MN1,PITPNB chr10 104:104.2 NFKB2,ELOVL3,PITX3,GBF1,PSD,FBXL15,CUEDC2,C10orf95,TMEM180,ACTR1A chr1 159.6:159.8 SDHC,C1orf192,FCGR2A,HSPA6,FCGR3A,FCGR2C chr1 11.6:11.8 FBXO2,FBXO44,FBXO6,MAD2L2,C1orf187,MTHFR,CLCN6,NPPA,NPPB,AGTRAP chr6 151:151.2 PLEKHG1,MTHFD1L chr10 91:91.2 LIPA,IFIT2,IFIT3,IFIT1L,IFIT5,SLC16A12,IFIT1,CH25H chr6 144.2:144.4 PHACTR2,LTV1,PLAGL1 chr14 100.8:101 chr7 44.2:44.6 GCK,YKT6,CAMK2B,NPC1L1,DDX56,TMED4,OGDH,NUDCD3 chr17 68.8:69 C17orf80,CDC42EP4,SDK2 chr3 156.2:156.4 MME,FLJ46120 chr11 29.8:30 KCNA4 chr11 11.4:11.6 GALNTL4 chr7 0.8:1 HEATR2,C7orf20,CENTA1,CYP2W1,MGC11257,FLJ44124,UNC84A,COX19 chr11 115.8:116 chr11 121.6:121.8 chr18 62.4:62.6 CDH19 chr14 74.8:75 FOS,JDP2 chr21 34:34.2 ITSN1,ATP5O chr10 9.6:9.8 chr6 165.4:165.6 C6orf118 chr14 73.2:73.4 ACOT6,DNAL1,PNMA1,C14orf43,ZADH1,ZNF410 chr5 91.8:92 chr12 16.6:16.8 LMO3 chr7 17.6:17.8 SNX13 chr9 138.4:138.6 SNAPC4,GPSM1,CARD9,SDCCAG3,PMPCA,INPP5E,C9orf163,NOTCH1,LOC728489,KIAA0310 chr22 20.2:20.4 LOC220686,LOC375133,UBE2L3,LOC150223,CCDC116,SDF2L1,PPIL2,YPEL1,MAPK1 chr11 61.2:61.4 C11orf11,C11orf9,C11orf10,FEN1,FADS1,FADS2,FADS3,RAB3IL1 chr9 99.6:99.8 ANP32B,C9orf156,FOXE1,HEMGN chr17 42.6:42.8 CDC27,MYL4,ITGB3,C17orf57 chr9 27.4:27.6 IFNK,MOBKL2B,C9orf72 chr11 34.2:34.4 ABTB2,CAT chr1 41.2:41.4 CTPS,SLFNL1,SCMH1 chr11 107.2:107.4 SLC35F2,RAB39,CUL5 chr7 43.4:43.6 C7orf44,HECW1,STK17A chr2 44:44.2 ABCG8,LRPPRC,PPM1B chr15 82.6:82.8 KIAA1920 chr8 135.2:135.4

Figure 21: The top 1% of XP-EHH signals in the Bantu, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 24 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001 chr6 164.6:164.8 chr10 9.6:9.8 chr17 0.6:0.8 VPS53,FAM57A,C17orf25,RNMTL1,NXN,TIMM22,GEMIN4 chr6 52:52.2 PKHD1,IL17A,IL17F,MCM3 chr8 106.4:106.6 ZFPM2 chr11 18.6:18.8 SPTY2D1,TMEM86A,IGSF22,PTPN5,UEVLD chr16 86.4:86.6 KLHDC4,SLC7A5,CA5A,BANP chr7 106.2:106.4 PIK3CG chr10 0.6:0.8 DIP2C,C10orf108,LARP5 chr19 52:52.4 SLC1A5,AP2S1,GRLF1,NPAS1,TMEM160,SAE1,BBC3,FKRP chr1 82.4:82.6 chr13 59.6:59.8 DIAPH3 chr11 34.2:34.4 ABTB2,CAT chr13 107.6:107.8 LIG4,ABHD13,TNFSF13B chr3 115.4:115.6 DRD3,ZNF80,VSIG9,ZBTB20 chr11 29.8:30 KCNA4 chr9 115:115.2 RGS3,SLC31A2,SLC31A1,CDC26,PRPF4,RNF183,WDR31,BSPRY,HDHD3,ALAD,POLE3,C9orf43 chr18 52:52.2 FLJ45743 chr22 38.4:38.6 CACNA1I,ENTHD1,GRAP2 chr18 44.8:45 DYM chr14 100.2:100.4 C14orf70,DLK1 chr9 25:25.2 chr1 198.6:198.8 ZNF281,KIF14 chr20 60.6:60.8 FLJ30313,C20orf166,SLCO4A1,NTSR1 chr8 126.8:127 chr3 2.4:2.6 CNTN4 chr5 178.2:178.4 GRM6,ZNF354B,ZFP2,ZNF454,ZNF354C chr11 32.4:32.6 WT1,WIT1,PCID1,CCDC73 chr15 49.4:49.6 GLDN,CYP19A1,DMXL2 chr16 27.6:27.8 KIAA0556,GSG1L chr17 58.8:59 CYB561,ACE,KCNH6,CCDC44,WDR68 chr8 0.2:0.4 C8orf42,ZNF596,FBXO25 chr4 4.6:4.8 STX18 chr19 48.4:48.6 PSG5,PSG4,PSG9,TEX101,CD177 chr8 125.4:125.6 TMEM65,TRMT12,RNF139,TATDN1,NDUFB9,MTSS1 chr6 20:20.2 MBOAT1 chr7 139.2:139.4 TBXAS1,PARP12,KIAA1718 chr11 63:63.2 HRASLS5,LGALS12,RARRES3,HRASLS2,HRASLS3,DKFZP564J0863,RTN3 chrX 91.6:91.8 PCDH11X chrX 115:115.2 AGTR2 chr14 94.6:94.8 DICER1,FLJ45244,CLMN chr19 56.8:57 ZNF175,SIGLEC5,HAS1,FPR1,FPRL1,FPRL2 chr22 15.4:15.6 CESK1,XKR3 chr9 134.8:135 C9orf9,TSC1,GFI1B,GTF3C5,CEL,RALGDS,GBGT1 chr5 177.4:177.6 LOC653316,PROP1,N4BP3,RMND5B,NOLA2,HNRPAB,AGXT2L2,COL23A1,LOC653314 chr17 76.6:76.8 KIAA1303,AZI1,CHMP6,BAIAP2,FLJ44861,C17orf56,MGC15523,AATK chr6 67.2:67.4 chr15 23.4:23.6 ATP10A chr10 104:104.2 NFKB2,ELOVL3,PITX3,GBF1,PSD,FBXL15,CUEDC2,C10orf95,TMEM180,ACTR1A chr11 94.8:95 chr11 13.6:13.8 MLSTD2 chr11 61.2:61.4 C11orf11,C11orf9,C11orf10,FEN1,FADS1,FADS2,FADS3,RAB3IL1 chr3 195.4:195.6 GP5,LRRC15,CPN2 chr9 132.8:133 LAMC3,ABL1,P518,FIBCD1,C9orf58,NUP214 chr13 106.6:106.8 LOC728215 chr3 121.8:122 NDUFB4,GTF2E1,HGD,RABL3 chr13 89.8:90 chr10 12.4:12.6 CAMK1D chr19 45.6:45.8 PLD3,HIPK4,SERTAD1,SERTAD3,BLVRB,SHKBP1,PRX,SPTBN4,LTBP4 chr12 66.2:66.4 DYRK2 chr3 156.2:156.4 MME,FLJ46120 chr17 21.2:21.6 MAP2K3,KCNJ12 chr7 153:153.2 DPP6,FLJ16734 0.05 chr2 11.8:12 LPIN1 chr1 238:238.2 CHRM3 chr22 34:34.2 HMG2L1,TOM1,HMOX1,MCM5 chr1 1.8:2.2 GNB1,CALML6,TMEM52,LOC339457,GABRD,PRKCZ,SKI,MORN1,C1orf86,KIAA1751 chr9 112.8:113 EDG2 chr2 183.4:183.6 DNAJC10,FRZB,NCKAP1 chr13 58.6:58.8 chr16 64:64.2 chr20 16.4:16.6 C20orf23 chr3 98.8:99 ARL6,EPHA6 chr1 57:57.2 C1orf168,C8A,C8B,DAB1 chr16 31.2:31.6 ITGAM,ITGAX,ITGAD,COX6A2,ARMC5,TGFB1I1,SLC5A2,C16orf58,ERAF chr6 26.4:26.6 HIST1H4G,HIST1H3F,HIST1H2BH,HIST1H3G,HIST1H2BI,HIST1H4H,BTN3A2,BTN2A2,BTN3A1,BTN2A3,BTN3A3,BTN2A1,BTN1A1,HMGN4 chr11 0.6:0.8 CEND1,C11orf35,RASSF7,KIAA1542,SCT,DRD4,DEAF1,EPS8L2,TALDO1,SLC25A22,LRDD,RPLP2,PNPLA2,EFCAB4A,CD151,POLR2L,TSPAN4,IRF7,MUCDHL,TMEM80,PDDC1 chr8 59.2:59.4 C8orf72 chr6 24:24.2 NRSN1 chr17 27.8:28 PSMD11,CDK5R1,MYO1D chr7 106.6:106.8 PRKAR2B,HBP1,COG5 chr14 43.6:43.8 chrX 41.6:41.8 CASK chr1 171.2:171.4 TNFSF18,TNFSF4 chr2 105.2:105.4 GPR45,TGFBRAP1,C2orf49,FHL2 chrX 102.8:103 TCEAL3,TCEAL1,MORF4L2,TMEM31,PLP1,RAB9B chr15 76.4:76.6 DNAJA4,WDR61,CRABP1,IREB2,LOC123688,PSMA4,CHRNA5 chr17 9:9.2 NTN1,STX8 chr1 12.2:12.4 TNFRSF1B,VPS13D chr4 13:13.2 RAB28,BAPX1,FAM44A chr12 29.8:30 TMTC1 chr5 56.8:57 DKFZp686D0972 chr20 34.8:35 NDRG3,DSN1,C20orf117,C20orf118,SAMHD1 chr11 133.2:133.4 SPATA19,JAM3 chr19 1:1.2 GRIN3B,C19orf6,CNN2,ABCA7,HMHA1,POLR2E,SBNO2,STK11,C19orf26,ATP5D,MIDN,C19orf23,CIRBP,C19orf24,EFNA2,GPX4 chr11 113.8:114 FAM55D,C11orf71,RBM7,REXO2,FAM55A chr2 171:171.2 MYO3B chr18 40.8:41 SETBP1 chr10 12:12.2 C10orf47,UPF2,DHTKD1,SEC61A2,NUDT5 chr6 148.8:149 SASH1 chr16 55.4:55.6 NLRC5,NUP93,SLC12A3,HERPUD1,CETP chr19 5.4:5.6 ZNRF4,PLAC2,SAFB,P117,HSD11B1L,RPL36,LONP1,SAFB2 chr8 109.6:109.8 TTC35 chr15 20.4:20.6 TUBGCP5,CYFIP1,NIPA2,NIPA1 chr17 64.8:65 ABCA10,ABCA5,MAP2K6 chr7 5.2:5.4 WIPI2,FBXL18,SLC29A4,KIAA1856 chr4 114.4:114.6 ANK2,CAMK2D chr19 38:38.2 SLC7A9,CCDC123,C19orf40,RHPN2 chr12 55.8:56 KIAA0286,STAT6,LRP1,NXPH4,SHMT2,NDUFA4L2,STAC3,R3HDM2,NAB2 chr1 158.4:158.6 ATP1A2,ATP1A4,CASQ1,PEA15,WDR42A,PEX19,COPA,NCSTN,NHLH1,VANGL2 chr3 9.2:9.4 SRGAP3,THUMPD3,SETD5 chr5 126.2:126.4 LMNB1,MARCH3 chr12 29:29.2 chr2 111.8:112 chr6 155:155.2 RBM16 chr18 5.2:5.4 ZFP161,EPB41L3 chr9 83.4:83.6 TLE1 chr12 102.6:102.8 STAB2,NT5DC3,HSP90B1 chr1 39.2:39.4 RHBDL2,C1orf108,NDUFS5,MACF1 chr3 12.8:13 TMEM40,RPL32,IQSEC1,CAND2 chr11 43.4:43.6 TTC17 chr7 155.4:155.6 chr19 0.4:0.6 MADCAM1,C19orf19,CDC34,GZMM,BSG,HCN2,POLRMT,FGF22,FLJ45684,RNF126,PRSSL1,C19orf20,FSTL3 chr21 43.2:43.4 WDR4,NDUFV3,PKNOX1,CBS,U2AF1 chr16 53.2:53.4

Figure 22: The top 1% of XP-EHH signals in the Biaka Pygmies, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 25 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001

chr21 16.8:17 C21orf34 chr15 46:46.4 SLC24A5,MYEF2,SLC12A1,DUT chr17 60.6:61 RGS9,AXIN2 chr9 90:90.4 SPIN1,C9orf121 chr3 131.4:131.8 FLJ35880 chr12 87.4:87.8 KITLG chr8 140:140.2 COL22A1 chr10 65.4:65.8 chr17 56.2:56.6 BCAS3 chr7 119.6:120 KCND2 chr18 11.2:11.4 chr14 61:61.2 PRKCH,HIF1A chr10 83.6:83.8 NRG3 chr4 82:82.4 C4orf22,BMP3,PRKG2 chr1 35.4:35.8 SFPQ,ZMYM4,KIAA0319L,NCDN,TFAP2E,PSMB2,ZMYM1 chr2 238:238.2 COL6A3,PRLH,RAB17,MLPH chr15 67.4:67.8 GLCE,PAQR5,KIF23,RPLP1,LOC729416 chr18 19.6:20 LAMA3,CABYR,OSBPL1A,C18orf17 chr6 0:0.2 DUSP22,FLJ43763 chr4 32.6:33 chr5 109.6:110 chr5 21.8:22 CDH12 chr7 18.6:18.8 HDAC9 chr3 72.6:72.8 RYBP chr5 26.4:26.8 chr3 25.8:26 NGLY1,OXSM chr4 55.8:56 SRD5A2L,TMEM165,CLOCK chr3 176.6:176.8 NAALADL2 chr5 74.4:74.8 GCNT4,HMGCR,COL4A3BP,POLK chr3 31.2:31.6 STT3B chr9 3.2:3.4 RFX3 chr12 2.6:2.8 FKBP4,ITFG2,NRIP2,FOXM1,CACNA1C chrX 110:110.4 PAK3,CAPN6,DCX chr4 172.6:172.8 chr20 58.2:58.4 LOC284757 chr4 5.2:5.4 STK32B chr14 62.8:63 RHOJ,GPHB5,PPP2R5E chr20 48.8:49 PARD6B,BCAS4,ADNP,DPM1,MOCS3 chr22 20.6:20.8 MAPK1,PPM1F,TOP3B chr15 89.8:90 chr10 84:84.2 NRG3 chr18 7.4:7.8 PTPRM chr20 52.4:52.6 DOK5 chr6 73.8:74 C6orf148,KCNQ5 chr1 244:244.2 SMYD3 chr1 36:36.4 FLJ38984,CLSPN,EIF2C4,EIF2C1,EIF2C3,TEKT2,ADPRHL2,COL8A2,TRAPPC3,MAP7D1 chr2 178:178.4 PDE11A,AGPS,TTC30A,TTC30B 0.05 chr4 60.8:61.2 chr17 55.6:56 CA4,USP32,C17orf64,APPBP2,PPM1D chr5 75:75.4 C5orf37,SV2C chr2 152.2:152.4 NEB,ARL5A,CACNB4 chr6 14.8:15 chr12 57.6:57.8 LRIG3 chr8 16.2:16.4 chr11 64:64.2 SLC22A11,SLC22A12,NRXN2 chr3 3.8:4 LRRN1 chr22 45:45.2 FLJ20699,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1 chr6 143:143.2 HIVEP2 chr10 22.4:22.8 COMMD3,BMI1,SPAG6 chr11 41.8:42 chr21 29.8:30.2 GRIK1 chr3 192:192.2 chr7 33.6:33.8 BBS9 chr10 118:118.4 GFRA1,C10orf96,PNLIPRP3,PNLIP,PNLIPRP1,C10orf82,PNLIPRP2,HSPA12A chrX 36:36.2 CXorf59 chr17 51.4:51.6 ANKFN1 chr15 46.6:46.8 CEP152,FBN1 chr7 37:37.2 ELMO1 chr16 64.6:64.8 chr5 90.4:90.6 GPR98 chr3 100.4:100.8 COL8A1 chr2 167.6:168 CMYA3 chr4 14.2:14.4 chr8 18.6:18.8 PSD3 chr4 33.2:33.6 chr15 27:27.4 APBA2,NDNL2 chr4 29.4:29.8 chr6 108:108.2 SCML4,FLJ10159 chr13 73.6:73.8 KLF12 chr19 7.2:7.6 ARHGEF18,PEX11G,C19orf45,ZNF358,MCOLN1,XAB2,PCP2,STXBP2,RETN,PNPLA6,C19orf59,INSR,KIAA1543 chr1 228:228.2 chr1 192.4:192.6 chr6 105.6:105.8 LIN28B,BVES,POPDC3,PREP chr1 160.2:160.4 ATF6,OLFML2B,NOS1AP chr18 64.8:65 CCDC102B chr6 75.6:75.8 chr6 124:124.2 TCBA1,TRDN chr15 57.2:57.4 RNF111,CCNB2,MYO1E,LDHAL6B chr2 120.8:121 RALB,INHBB chr2 222.2:222.4 chrX 98.4:98.6 chr1 234.8:235 LGALS8,HEATR1,ACTN2,MTR

Figure 23: The top 1% of XP-EHH signals in Europe, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 26 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001

chr21 16.8:17 C21orf34 chr15 46:46.4 SLC24A5,MYEF2,SLC12A1,DUT chr8 140:140.2 COL22A1 chr22 45:45.2 FLJ20699,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1 chr6 0:0.2 DUSP22,FLJ43763 chr14 62.6:63 KCNH5,RHOJ,GPHB5,PPP2R5E chr17 56:56.4 APPBP2,PPM1D,BCAS3 chr5 26.4:26.8 chr14 61:61.2 PRKCH,HIF1A chr8 139.6:139.8 C8ORFK32,COL22A1 chr12 87.2:87.6 KITLG chr3 25.6:26 RARB,TOP2B,NGLY1,OXSM chr7 119.4:119.8 KCND2 chr11 8:8.2 EIF3S5,TUB,RIC3,LMO1 chr10 65.4:65.8 chr15 46.6:46.8 CEP152,FBN1 chr5 109.6:110 chr2 238:238.2 COL6A3,PRLH,RAB17,MLPH chr3 31.2:31.6 STT3B chr18 55.8:56 chr6 108:108.2 SCML4,FLJ10159 chr15 27:27.4 APBA2,NDNL2 chr5 23.2:23.6 PRDM9 chr20 52.4:52.6 DOK5 chr6 123.8:124.2 TCBA1,TRDN chr17 52.6:53 AKAP1,MSI2 chr10 22.2:22.6 COMMD3,DNAJC1 chr9 1.8:2 SMARCA2 chr19 7.2:7.6 ARHGEF18,PEX11G,C19orf45,ZNF358,MCOLN1,XAB2,PCP2,STXBP2,RETN,PNPLA6,C19orf59,INSR,KIAA1543 chrX 110:110.4 PAK3,CAPN6,DCX chrX 35.8:36.2 CXorf59,CXorf22 chr10 118:118.4 GFRA1,C10orf96,PNLIPRP3,PNLIP,PNLIPRP1,C10orf82,PNLIPRP2,HSPA12A chr8 17.6:17.8 MTUS1,FGL1,PCM1 chr21 29.8:30.2 GRIK1 chr3 131.6:131.8 FLJ35880 chr1 35.2:35.6 SFPQ,ZMYM4,ZMYM1,ZMYM6 chr1 35.8:36.2 KIAA0319L,NCDN,TFAP2E,PSMB2,FLJ38984,CLSPN,EIF2C4,EIF2C1,EIF2C3 chr16 77:77.2 WWOX chr7 33.6:33.8 BBS9 chr12 57.6:57.8 LRIG3 chr3 26.2:26.4 chr15 67.6:67.8 chr12 124.6:124.8 TMEM132B chr11 64:64.4 SLC22A11,SLC22A12,NRXN2,RASGRP2,PYGM,SF1,MAP4K2,MEN1,CDC42BPG,EHD1,KIAA0404,PPP2R5B chr1 65:65.2 RAVER2,JAK1 chr9 32.6:32.8 NDUFB6,TAF1L,LOC401498 chr1 192.2:192.6 0.05 chr3 112.6:112.8 CD96,ZBED2 chr6 14.8:15 chr18 19.8:20 LAMA3,CABYR,OSBPL1A,C18orf17 chr6 73.8:74 C6orf148,KCNQ5 chr10 25.8:26 GPR158 chr3 113:113.2 TMPRSS7,PLCXD2,PHLDB2,ABHD10,TAGLN3 chr3 100.4:100.8 COL8A1 chr10 22.8:23 PIP5K2A chr5 21.8:22 CDH12 chr4 55.8:56 SRD5A2L,TMEM165,CLOCK chr18 7.4:7.6 PTPRM chr4 172.6:172.8 chr9 90.2:90.4 SPIN1,C9orf121 chr2 222.2:222.4 chr17 60.6:60.8 RGS9 chr20 21.8:22 chr16 1.8:2 RNF151,MAPK8IP3,NME3,MRPS34,EME2,SPSB3,NUBP2,IGFALS,FAHD1,C16orf73,SEPX1,RPL3L,NDUFB10,RPS2,TBL3,NOXO1,GFER,SYNGR3,ZNF598,SLC9A3R2,NTHL1,HAGH,TSC2,LOC91561,HS3ST6 chr13 103:103.2 chr9 107:107.2 SLC44A1 chr2 213:213.2 ERBB4 chr10 83.6:84 NRG3 chr3 111.2:111.4 chr13 33.4:33.6 RFC3 chr4 60.8:61 chr5 19.6:19.8 CDH18 chr20 15.6:15.8 C20orf133 chr1 246:246.2 OR5AT1,OR11L1,OR2W3,OR2T8,OR2L13,OR2L8,OR2AK2,TRIM58,OR1C1,OR5AY1 chr1 244:244.2 SMYD3 chr6 105.6:105.8 LIN28B,BVES,POPDC3,PREP chr12 87.8:88 chr17 51.4:51.6 ANKFN1 chr4 170.4:170.6 SH3RF1,NEK1 chr20 48.8:49 PARD6B,BCAS4,ADNP,DPM1,MOCS3 chr3 176.6:176.8 NAALADL2 chr8 116:116.2 chr11 103.8:104 chr6 128.8:129 PTPRK chr6 4.6:4.8 KU−MEL−3,CDYL chr9 16:16.2 C9orf93 chr5 11.6:11.8 CTNND2 chr12 125.6:125.8 chr2 152.2:152.4 NEB,ARL5A,CACNB4 chr11 87:87.2 chr5 24.6:24.8 CDH10 chr4 33.4:33.6 chr4 14.2:14.4

Figure 24: The top 1% of XP-EHH signals in the Middle East, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 27 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001

chr22 45:45.2 FLJ20699,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1 chr7 119.4:119.8 KCND2 chr3 176.6:177 NAALADL2 chr21 16.8:17 C21orf34 chr15 46:46.4 SLC24A5,MYEF2,SLC12A1,DUT chr17 60.6:60.8 RGS9 chr4 29.4:29.8 chr17 56.2:56.6 BCAS3 chr12 87.4:87.8 KITLG chr3 25.6:26 RARB,TOP2B,NGLY1,OXSM chr16 84.4:84.6 COX4NB,COX4I1,IRF8 chr17 50.8:51.2 HLF,MMD,TMEM100,PCTP chr20 52.4:52.6 DOK5 chr6 105.6:105.8 LIN28B,BVES,POPDC3,PREP chr10 65.4:65.8 chr15 46.6:46.8 CEP152,FBN1 chr12 2.6:2.8 FKBP4,ITFG2,NRIP2,FOXM1,CACNA1C chr6 0:0.2 DUSP22,FLJ43763 chr4 41.8:42 SLC30A9,CCDC4 chr10 84:84.2 NRG3 chr17 52:52.2 NOG chr9 32.6:32.8 NDUFB6,TAF1L,LOC401498 chr10 22.4:22.8 COMMD3,BMI1,SPAG6 chr10 59.2:59.4 chr14 62.6:63 KCNH5,RHOJ,GPHB5,PPP2R5E chr10 100.2:100.4 C10orf33,HPS1,HPSE2 chr12 57.6:57.8 LRIG3 chr7 118.2:118.6 chr2 178:178.4 PDE11A,AGPS,TTC30A,TTC30B chrX 110:110.4 PAK3,CAPN6,DCX chr20 48.8:49 PARD6B,BCAS4,ADNP,DPM1,MOCS3 chr8 139.6:140 C8ORFK32,COL22A1 chr3 26.2:26.4 chr12 125.6:125.8 chr3 31.2:31.6 STT3B chr9 90.2:90.4 SPIN1,C9orf121 chr4 82.2:82.4 BMP3,PRKG2 chr22 20.6:20.8 MAPK1,PPM1F,TOP3B chr15 27:27.4 APBA2,NDNL2 chr10 83.6:83.8 NRG3 chr4 55.8:56 SRD5A2L,TMEM165,CLOCK chr21 16.2:16.6 USP25,C21orf34 chr7 18.6:18.8 HDAC9 chr4 5.2:5.4 STK32B chr11 109.2:109.4 chr7 118.8:119.2 0.05 chr5 109.6:110 chr9 3.2:3.4 RFX3 chr11 87:87.4 chr21 15.8:16 USP25 chr2 218.8:219 GPBAR1,PNKD,ARPC2,TMBIM1,MGC50811,SLC11A1,CTDSP1,VIL1,USP37,AAMP chr7 145.4:145.8 CNTNAP2 chr6 143:143.2 HIVEP2 chr17 55.6:56 CA4,USP32,C17orf64,APPBP2,PPM1D chr4 84.2:84.4 LIN54,COPS4,PLAC8,HPSE,COQ2 chr12 126.8:127 chr1 35.6:35.8 ZMYM4,KIAA0319L,NCDN,TFAP2E,PSMB2 chr6 73.8:74 C6orf148,KCNQ5 chr2 237.6:237.8 COPS8 chr12 65.6:66 CAND1 chr5 26.4:26.6 chr15 67.6:67.8 chrX 111:111.2 ZCCHC16,TRPC5 chr8 11:11.2 C8orf15,MTMR9,AMAC1L2,XKR6 chr13 91.2:91.6 GPC5 chr8 37:37.2 chr18 64.8:65 CCDC102B chr15 33.6:33.8 ATPBD4 chr17 52.6:52.8 AKAP1,MSI2 chr11 129.4:129.6 PRDM10,C11orf37,APLP2,ST14,ZBTB44 chr9 107:107.2 SLC44A1 chr2 205.8:206 PARD3B chr1 203:203.2 NFASC chr1 36.2:36.4 EIF2C1,EIF2C3,TEKT2,ADPRHL2,COL8A2,TRAPPC3,MAP7D1 chr12 116.4:116.6 KSR2 chr2 231.4:231.6 GPR55,CAB39,ITM2C,PSMD1 chr3 142.2:142.6 SLC25A36,SPSB4,ACPL2,ZBTB38 chr17 11:11.2 FLJ45455 chr3 167:167.2 BCHE chr10 118:118.2 GFRA1,C10orf96,PNLIPRP3 chr21 29.8:30 GRIK1 chr13 32.2:32.4 APRIN chr4 33.4:33.6 chr1 187.4:187.6 chr13 103:103.2 chr3 43.2:43.4 TMEM16K,SNRK chr10 59.6:59.8 IPMK,ZCD1,UBE2D1,TFAM chr17 51.4:51.6 ANKFN1 chrX 110.6:110.8 ALG13 chr18 11.2:11.4 chr2 192:192.2 MYO1B

Figure 25: The top 1% of XP-EHH signals in South Asia, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 28 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001 chr11 25.2:25.6 chr15 61.4:61.8 APH1B,CA12,USP3,FBXL22,HERC1 chr2 177:177.4 chr22 21.6:21.8 RTDR1,GNAZ,RAB36 chr4 158.6:159 chr22 45:45.2 FLJ20699,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1 chr17 56.2:56.6 BCAS3 chr4 5.8:6.2 EVC2,CRMP1,FLJ46481,JAKMIP1,EVC chr8 139:139.2 C8ORFK32 chr2 9.2:9.6 ITGB1BP1,DDEF2,CPSF3,IAH1,ADAM17,YWHAQ chr3 26.2:26.4 chr3 176.6:177 NAALADL2 chr21 16.2:16.6 USP25,C21orf34 chr2 125.4:125.8 CNTNAP5 chr2 198.6:199 PLCL1 chr2 17.8:18 SMC6,FLJ40869,KCNS3 chr2 108.8:109 RANBP2,FLJ32745,EDAR chr16 64.2:64.6 chr4 159.2:159.4 C4orf18,TMEM144 chr20 58.2:58.4 LOC284757 chr2 17.2:17.6 VSNL1 chr10 59.2:59.4 chr8 10.8:11.2 C8orf15,MTMR9,AMAC1L2,XKR6 chr3 25.6:26 RARB,TOP2B,NGLY1,OXSM chr1 103.2:103.6 COL11A1 chrX 110:110.4 PAK3,CAPN6,DCX chr6 105.6:106 LIN28B,BVES,POPDC3,PREP chr21 41.4:41.6 PLAC4,BACE2,FAM3B chr10 94.4:94.8 KIF11,HHEX,EXOC6,CYP26C1,CYP26A1 chr17 53.2:53.6 OR4D2,MRPS23,CUEDC1,VEZF1,DYNLL2,OR4D1,EPX,MKS1,SFRS1 chr5 117.2:117.6 chr1 170.8:171.2 C1orf9,FASLG chr7 135.4:135.6 chr2 126:126.2 chr4 41.4:41.8 DKFZP686A01247,PHOX2B,TMEM33,WDR21B,SLC30A9,CCDC4 chr1 64:64.4 ROR1,UBE2U chr4 144.4:144.6 USP38,GAB1 chr4 7.6:7.8 AFAP1,SORCS2 chr4 143.8:144.2 chr12 125.4:125.8 0.05 chr2 108.2:108.6 SULT1C3,SULT1C1,SULT1C2,GCC2,LIMS1 chr14 68.6:68.8 WDR22,EXDL2,GALNTL1 chr4 84.2:84.4 LIN54,COPS4,PLAC8,HPSE,COQ2 chr3 108.8:109.2 BBX,CD47 chr3 44.6:45 ZNF167,ZNF660,ZNF197,ZNF35,ZNF502,ZNF501,KIAA1143,KIF15,TMEM42,TGM4,ZDHHC3,EXOSC7,CLEC3B chr15 62:62.2 DAPK2,FAM96A,SNX1,SNX22,PPIB,CSNK1G1 chr7 112:112.4 TMEM168,FLJ31818 chr2 43.4:43.8 THADA,PLEKHH2 chr6 129.4:129.6 LAMA2 chr7 3.8:4.2 SDK1 chr10 55.6:55.8 PCDH15 chr21 16.8:17 C21orf34 chr2 212.8:213.2 ERBB4 chr4 168.8:169.2 chr4 170.8:171 NEK1,CLCN3,C4orf27 chr8 135:135.4 chrX 111:111.2 ZCCHC16,TRPC5 chr17 55.6:55.8 CA4,USP32 chr5 117.8:118 chr6 4.8:5 CDYL,RPP40 chr3 103.6:103.8 ZPLD1 chr7 29.8:30 SCRN1,FKBP14,PLEKHA8,WIPF3 chr20 30:30.4 TTLL9,PDRG1,XKR7,C20orf160,HCK,TM9SF4,PLAGL2,POFUT1,KIF3B,ASXL1 chr1 232.8:233 IRF2BP2 chr9 32.6:32.8 NDUFB6,TAF1L,LOC401498 chr6 125.8:126 chr4 191:191.2 DUX4,FRG1,TUBB4Q,DUX4C,FRG2 chr11 60.2:60.4 MS4A8B,MGC35295,MS4A10,CCDC86,GPR44,ZP1,PRPF19,TMEM109,TMEM132A chr1 8.2:8.6 RERE,SLC45A1 chr4 28.4:28.6 chr2 25.8:26 DTNB,ASXL2,KIF3C chr4 170.4:170.6 SH3RF1,NEK1 chr15 62.6:62.8 ZNF609,OAZ2,RBPMS2 chr9 13.8:14 chr12 87.6:87.8 chr15 44:44.2 chr12 122.6:122.8 FLJ39378,DDX55,EIF2B1,GTF2H3,C12orf38,ATP6V0A2,DNAH10,TMED2 chrX 110.6:110.8 ALG13 chr3 187.4:187.6 DGKG

Figure 26: The top 1% of XP-EHH signals in East Asia, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 29 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001

chr22 21.6:21.8 RTDR1,GNAZ,RAB36 chr2 177.8:178.2 HNRPA3,PDE11A,NFE2L2,AGPS,TTC30A,TTC30B chr22 46.4:46.6 FLJ46257 chr2 178.4:178.8 DRB1,PDE11A,OSBPL6 chr4 158.2:158.6 GLRB,GRIA2 chr10 59.2:59.4 chr12 125.4:125.8 chr4 158.8:159 chr17 56.2:56.6 BCAS3 chr3 157.2:157.6 KCNAB1 chr22 45:45.2 FLJ20699,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1 chr10 115:115.4 HABP2,NRAP,CASP7 chr2 158.2:158.6 ACVR1C,ACVR1,UPP2 chr16 11:11.4 PRM1,KIAA0350,SOCS1,TNP2,PRM3,PRM2,C16orf75,LOC400499 chr19 46.6:46.8 TGFB1,MGC4093,EXOSC5,BCKDHA,B3GNT8,FLJ10241,CEACAM21,CEACAM4,TMEM91 chr5 107.2:107.6 FBXL17 chr12 1:1.4 ERC1 chr15 58.2:58.4 ANXA2 chr5 169:169.2 CCDC99,DOCK2 chr6 48.6:49 chr12 30.4:30.6 chr5 154.6:155 chr6 49.2:49.4 chr1 165.2:165.6 C1orf32,MAEL,GPA33,POU2F1,DUSP27 chr2 108.4:108.8 SULT1C2,GCC2,LIMS1,RANBP2,FLJ32745 chr12 26:26.4 RASSF8,BHLHB3,SSPN,ITPR2 chr6 105.8:106.2 PREP chr7 145.4:145.8 CNTNAP2 chrX 110:110.4 PAK3,CAPN6,DCX chr15 43.8:44.2 SQRDL chr21 14.8:15 SAMSN1 chr6 111:111.4 CDC2L6,AMD1,C6orf51,BXDC1 chr21 16.2:16.6 USP25,C21orf34 chr5 140.6:141 PCDHB9,PCDHB10,PCDHB11,PCDHB12,PCDHB13,PCDHB14,PCDHB15,SLC25A2,TAF7,PCDHGA1,PCDHGA2,PCDHGA3,PCDHGB1,PCDHGA4,PCDHGB2,PCDHGA5,PCDHGB3,PCDHGA6,PCDHGA7,PCDHGB4,PCDHGA8,PCDHGB5,PCDHGA9,PCDHGB6,PCDHGA10,PCDHGB7,PCDHGA11,PCDHGA12,PCDHGC3,PCDHGC4,PCDHGC5,HDAC3,C5orf16,FCHSD1,CENTD3,DIAPH1 chr5 153.6:153.8 GALNT10,SAP30L,HAND1 chr6 134.6:135 chr20 32.6:33 ACSS2,ITCH,DYNLRB1,MAP1LC3A,PIGU,TP53INP2,NCOA6,GSS,MYH7B,GGTL3 chr1 178:178.4 C1orf76,TOR1AIP2,IFRG15,TOR1AIP1,QSCN6,CEP350 chr4 61.4:61.6 chr22 39.4:39.8 MKL1,MCHR1,SLC25A17,ST13,XPNPEP3,DNAJB7,RBX1,EP300 chr10 2.8:3 chr2 158.8:159.2 LOC130940,PKP4 0.05 chr6 35.2:35.4 ANKS1A,TCP11,SCUBE3,ZNF76,DEF6,PPARD chr8 11:11.2 C8orf15,MTMR9,AMAC1L2,XKR6 chr5 108:108.2 FER chr18 11.2:11.4 chr22 40:40.2 L3MBTL2,RANGAP1,ZC3H7B,TEF,TOB2,PHF5A,ACO2 chr22 48.2:48.4 FLJ44385,C22orf34 chr5 173.2:173.4 CPEB4,HMP19 chr3 190:190.2 LPP chr6 125.8:126 chr2 3.6:3.8 RNASEH1,RPS7,COLEC11,ALLC chr2 28.2:28.6 BRE,FOSL2,PLB1 chr10 110:110.2 chr9 122.4:122.6 FBXW2,CDK5RAP2,PSMD5,MEGF9 chr6 162:162.2 PARK2 chrX 111:111.2 ZCCHC16,TRPC5 chr11 46.4:46.6 DGKZ,MDK,CHRM4,FLJ20294,C11orf77,KIAA0652 chr3 158:158.2 FLJ16641 chr5 8.6:8.8 chr10 59.6:59.8 IPMK,ZCD1,UBE2D1,TFAM chr4 60.8:61.2 chr11 92.8:93 C11orf75,CCDC67 chr2 17.6:18 VSNL1,SMC6,FLJ40869,KCNS3 chr2 9.4:9.8 ITGB1BP1,DDEF2,CPSF3,IAH1,ADAM17,YWHAQ chr4 160.6:160.8 chr5 150.4:150.6 TNIP1,ANXA6,CCDC69,GM2A,SLC36A3,GPX3 chr10 22.8:23 PIP5K2A chr1 27.6:27.8 FGR,SYTL1,MAP3K6,FCN3,GPR3,WASF2,AHDC1,CD164L2 chr6 54.6:55 FAM83B chr22 43:43.2 chr21 16.8:17 C21orf34 chr4 29.4:29.6 chr13 79.4:79.6 chr7 135.4:135.6 chr2 161.2:161.4 chr2 27.8:28 SLC4A1AP,RBKS,BRE,MRPL33 chr6 155.6:155.8 TIAM2,TFB1M,CLDN20,NOX3 chr12 87.6:87.8 chr11 25.4:25.6 chr19 23:23.2 chr3 24:24.2 NR1D2,THRB chr2 127.8:128 ERCC3,MAP3K2,IWS1,PROC,MYO7B chr5 134.6:134.8 H2AFY,C5orf20

Figure 27: The top 1% of XP-EHH signals in the Americas, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 30 BiakaPygmyBantuEuropeMideastS.AsiaE.AsiaOceaniaAmerica 0.001

chr22 44.8:45.2 FLJ20699,WNT7B,FLJ27365,PPARA,LOC150383,PKDREJ,GTSE1,TRMU,CELSR1,C22orf26 chr6 105.2:105.6 HACE1,LIN28B chr12 65.6:66 CAND1 chr21 16.2:16.6 USP25,C21orf34 chr4 95:95.4 ATOH1,SMARCAD1,PGDS chr8 100:100.4 OSR2,VPS13B chr8 19.4:19.8 ChGn,INTS10,LPL chr9 38:38.4 SHB,ALDH1B1,IGFBPL1 chr1 174.8:175.2 ASTN1,PAPPA2 chr5 58.6:59 PDE4D chr8 134.8:135.2 chr6 105.8:106 PREP chr4 170.8:171.2 NEK1,CLCN3,C4orf27,MFAP3L,AADAT chr4 170.2:170.6 CBR4,SH3RF1,NEK1 chr1 113.2:113.6 LRIG2,SLC16A1 chr2 22.2:22.6 chr20 5.8:6 C20orf196,CHGB,CGI−09,MCM8,CRLS1,C20orf75,C20orf42 chr4 55.8:56.2 SRD5A2L,TMEM165,CLOCK,PDCL2,NMU chr5 59.8:60.2 DEPDC1B,ELOVL7,ERCC8 chr22 24.8:25 MYO18B,SEZ6L chr4 85.2:85.6 NKX6−1 chrX 110:110.4 PAK3,CAPN6,DCX chr4 95.6:95.8 PDLIM5 chr2 237:237.4 CXCR7,IQCA chr11 120.6:121 TECTA,SORL1,SC5DL chr2 20.2:20.6 SDC1,PUM2,RHOB chr5 59.2:59.6 chr12 116.4:116.6 KSR2 chr21 17.6:17.8 CXADR chr4 159.6:159.8 RXFP1,LOC201725,PPID,ETFDH chr11 25.2:25.6 chr11 30.8:31.2 DCDC5,DCDC1 chr2 165.8:166.2 SCN2A,SCN3A,FAM130A2 chr11 31.4:31.8 DPH4,IMMP1L,PAX6,ELP4 chr12 92.8:93 CRADD chr2 212.8:213.2 ERBB4 chr8 63.6:64 FAM77D chr4 160:160.4 FLJ25371 0.05 chr2 2.8:3.2 TSSC1 chr3 71.4:71.8 FOXP1,EIF4E3 chr17 50.8:51 HLF,MMD chr2 142.6:143 LRP1B chr18 11.6:11.8 GNAL,CHMP1B chr22 40.4:40.6 MEI1,XRCC6,NHP2L1,FLJ23584,CCDC134,SREBF2 chr4 186.6:186.8 ANKRD37,C4orf20,CCDC110,PDLIM3,SORBS2 chr7 29.8:30 SCRN1,FKBP14,PLEKHA8,WIPF3 chrX 111:111.2 ZCCHC16,TRPC5 chr8 11:11.2 C8orf15,MTMR9,AMAC1L2,XKR6 chr8 100.6:100.8 VPS13B chr9 0.8:1 DMRT1,DMRT3,DMRT2 chr10 65.6:66 chr16 60:60.2 CDH8 chr5 30.6:30.8 chr13 110.4:110.8 ANKRD10,ARHGEF7,C13orf16 chr7 142:142.2 PRSS1,PRSS2 chr5 170.2:170.6 GABRP,RANBP17 chr10 6.8:7.2 SFMBT2 chr16 5.4:5.6 chr2 205.8:206 PARD3B chr16 77.2:77.4 WWOX chr11 44:44.2 LOC390110,PHACS,EXT2,ALX4 chr18 11.2:11.4 chr3 179.2:179.4 chr2 64.2:64.4 PELI1 chr8 99.6:99.8 STK3 chr22 39.8:40.2 EP300,L3MBTL2,RANGAP1,ZC3H7B,TEF,TOB2,PHF5A,ACO2 chr2 126:126.2 chr21 16.8:17 C21orf34 chr1 203.4:203.8 RBBP5,RIPK5,TMCC2,NUAK2,KLHDC8A,LEMD1,PCTK3,MFSD4 chr13 43.6:43.8 C13orf21 chr8 64.6:64.8 chrX 110.6:110.8 ALG13 chr10 9:9.2 chr5 99.4:99.6 chr2 232.2:232.4 MGC35154,PTMA,PDE6D,COPS7B chr20 0:0.2 DEFB125,DEFB126,DEFB127,DEFB128,DEFB129,DEFB32,C20orf96,ZCCHC3

Figure 28: The top 1% of XP-EHH signals in Oceania, ordered from top to bottom in order of signiﬁcance. See the caption of Figure 1 in the main text for details. 31 References

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