Supplementary information for Common risk variants identified in autism spectrum disorder November 22, 2017 Contents List of Supplementary Tables 2 List of Supplementary Figures 3 1 Sample description and data processing7 1.1 The iPSYCH ASD sample............................................7 1.1.1 The iPSYCH sample..........................................7 1.1.2 The iPSYCH ASD GWAS sample...................................7 1.1.3 Genotyping and calling........................................8 1.1.4 QC and Imputation...........................................8 1.1.5 PCA...................................................9 1.2 The PGC ASD sample.............................................9 1.3 The follow-up samples............................................. 10 1.3.1 deCODE................................................. 10 1.3.2 Finnish autism case-control study.................................. 10 1.3.3 PAGES.................................................. 10 1.3.4 BUPGEN................................................. 11 1.3.5 Follow-up sample summary...................................... 12 2 Methods 13 2.1 GWAS....................................................... 13 2.1.1 SNP-wise analysis........................................... 13 2.1.2 Gene-based association and gene-set analyses........................... 13 2.1.3 MTAG analyses............................................. 13 2.1.4 Mini-reviews.............................................. 14 2.2 SNP heritability................................................. 14 2.3 Genetic correlation and prediction...................................... 15 2.3.1 Polygenic risk scores.......................................... 15 2.4 Hi-C analysis.................................................. 17 3 Supplementary tables 18 3.1 GWAS....................................................... 18 1 2 3.1.1 Look-up tables for tophits in related phenotypes.......................... 28 3.2 Heritability.................................................... 32 3.3 Genetic correlation and prediction...................................... 32 3.4 Hi-C........................................................ 41 4 Supplementary figures 69 4.1 Sample description............................................... 69 4.2 GWAS....................................................... 69 4.2.1 Qq plots................................................. 69 4.2.2 Forest plots............................................... 70 4.2.3 Regional plots.............................................. 76 4.2.4 Gene-based association........................................ 85 4.2.5 MTAG analyses............................................. 99 4.3 Heritability.................................................... 104 4.4 Genetic correlation and prediction...................................... 107 4.5 HiC analysis................................................... 111 Bibliography 112 Supplementary Notes 125 Consortium Membership............................................... 125 Major Depressive Disorder Working Group of the PGC.......................... 125 The 23andMe Research Team......................................... 131 Acknowledgements.................................................. 131 List of Supplementary Tables S1.1.1 Descriptive table..............................................8 S1.3.1 Available data in PAGES.......................................... 11 S1.3.2 Key numbers for follow-up........................................ 12 S2.3.1 Hierarchical ASD subtypes........................................ 16 S2.3.2 Make-up of wave group for internal scoring.............................. 17 S3.1.1 Summary of top 20 ASD associations.................................. 18 S3.1.2 Top 25 genes of MAGMA analysis.................................... 19 S3.1.3 Mini review of top hits........................................... 20 S3.1.4 Gene set analysis of candidate gene sets................................. 28 S3.1.5 Top 25 gene set from analysis from MsigDB............................... 28 S3.1.6 Look-up of top schizophrenia loci in the ASD scan........................... 28 S3.1.7 Look-up of top major depression loci in the ASD scan......................... 30 S3.1.8 Look-up of top educational attainment loci in the ASD scan..................... 31 S3.2.1 Heritability estimates for subtypes and substrata............................ 32 S3.3.1 GCTA based rG between ASD subtypes................................. 33 S3.3.2 Genetic correlation output from LD Hub for ASD........................... 34 S3.4.1 Credible SNPs and Hi-C identified genes................................ 42 3 List of Supplementary Figures S1.1.1 Plot of the first two principal components................................9 S4.2.1 Qq plot for the iPSYCH ASD GWAS................................... 69 S4.2.2 Qq plot for iPSYCH-PGC meta analysis................................. 70 S4.2.3 Forest plot for rs910805 for the iPSYCH-PGC meta analysis...................... 70 S4.2.4 Forest plot for rs10099100 for the iPSYCH-PGC meta analysis.................... 70 S4.2.5 Forest plot for rs71190156 for the iPSYCH-PGC meta analysis.................... 71 S4.2.6 Forest plot for rs6047270 for the iPSYCH-PGC meta analysis..................... 71 S4.2.7 Forest plot for rs111931861 for the iPSYCH-PGC meta analysis.................... 71 S4.2.8 Forest plot for rs2391769 for the iPSYCH-PGC meta analysis..................... 71 S4.2.9 Forest plot for rs138867053 for the iPSYCH-PGC meta analysis.................... 72 S4.2.10 Forest plot for rs183563276m for the iPSYCH-PGC meta analysis................... 72 S4.2.11 Forest plot for rs1452075 for the iPSYCH-PGC meta analysis..................... 72 S4.2.12 Forest plot for rs1222063 for the iPSYCH-PGC meta analysis..................... 72 S4.2.13 Forest plot for rs142920272 for the iPSYCH-PGC meta analysis.................... 73 S4.2.14 Forest plot for rs55962189 for the iPSYCH-PGC meta analysis.................... 73 S4.2.15 Forest plot for rs112635299 for the iPSYCH-PGC meta analysis.................... 73 S4.2.16 Forest plot for rs6701243 for the iPSYCH-PGC meta analysis..................... 73 S4.2.17 Forest plot for rs45595836 for the iPSYCH-PGC meta analysis.................... 74 S4.2.18 Forest plot for rs325485 for the iPSYCH-PGC meta analysis...................... 74 S4.2.19 Forest plot for rs201910565 for the iPSYCH-PGC meta analysis.................... 74 S4.2.20 Forest plot for rs210894m for the iPSYCH-PGC meta analysis..................... 74 S4.2.21 Forest plot for rs72934503 for the iPSYCH-PGC meta analysis.................... 75 S4.2.22 Forest plot for rs11185408 for the iPSYCH-PGC meta analysis.................... 75 S4.2.23 Forest plot for rs141455452 for the iPSYCH-PGC meta analysis.................... 75 S4.2.24 Forest plot for rs78827416 for the iPSYCH-PGC meta analysis.................... 75 S4.2.25 Forest plot for rs59566011 for the iPSYCH-PGC meta analysis.................... 76 S4.2.26 Regional plot around rs910805, rs6047270 & rs55962189 for iPSYCH-PGC meta analysis..... 76 S4.2.27 Regional plot around rs10099100 for iPSYCH-PGC meta analysis.................. 77 S4.2.28 Regional plot around rs71190156 for iPSYCH-PGC meta analysis.................. 77 S4.2.29 Regional plot around rs111931861 for iPSYCH-PGC meta analysis.................. 78 4 5 S4.2.30 Regional plot around rs2391769 for iPSYCH-PGC meta analysis................... 78 S4.2.31 Regional plot around rs138867053 for iPSYCH-PGC meta analysis.................. 79 S4.2.32 Regional plot around rs183563276m for iPSYCH-PGC meta analysis................ 79 S4.2.33 Regional plot around rs1452075 for iPSYCH-PGC meta analysis................... 80 S4.2.34 Regional plot around rs1222063 & rs201910565 for iPSYCH-PGC meta analysis.......... 80 S4.2.35 Regional plot around rs142920272 & rs141455452 for iPSYCH-PGC meta analysis......... 81 S4.2.36 Regional plot around rs112635299 for iPSYCH-PGC meta analysis.................. 81 S4.2.37 Regional plot around rs6701243 for iPSYCH-PGC meta analysis................... 82 S4.2.38 Regional plot around rs45595836 for iPSYCH-PGC meta analysis.................. 82 S4.2.39 Regional plot around rs325485 for iPSYCH-PGC meta analysis.................... 83 S4.2.40 Regional plot around rs210894m for iPSYCH-PGC meta analysis.................. 83 S4.2.41 Regional plot around rs72934503 for iPSYCH-PGC meta analysis.................. 84 S4.2.42 Regional plot around rs11185408 for iPSYCH-PGC meta analysis.................. 84 S4.2.43 Regional plot around rs78827416 for iPSYCH-PGC meta analysis.................. 85 S4.2.44 Regional plot around rs59566011 for iPSYCH-PGC meta analysis.................. 85 S4.2.45 Qq plot for gene-based analysis...................................... 86 S4.2.46 Regional plot around XRN2 for gene-based analysis of iPSYCH-PGC meta............. 86 S4.2.47 Regional plot around KCNN2 for gene-based analysis of iPSYCH-PGC meta............ 87 S4.2.48 Regional plot around KIZ for gene-based analysis of iPSYCH-PGC meta.............. 88 S4.2.49 Regional plot around KANSL1 for gene-based analysis of iPSYCH-PGC meta........... 88 S4.2.50 Regional plot around MACROD2 for gene-based analysis of iPSYCH-PGC meta.......... 89 S4.2.51 Regional plot around WNT3 for gene-based analysis of iPSYCH-PGC meta............. 89 S4.2.52 Regional plot around MAPT for gene-based analysis of iPSYCH-PGC meta............ 90 S4.2.53 Regional plot around MFHAS1 for gene-based analysis of iPSYCH-PGC meta........... 90 S4.2.54 Regional