Supplementary Material

Supplementary Material.

TWAS-significant genes known to be in AD risk genes from GWAS

APOE The APOE gene encodes apolipoprotein E which binds fat to form lipoproteins. Its association with AD is well established through GWAS (Farrer et al., 1997) and being a carrier of the E4 allele of the APOE gene is one of the strongest risk factors for AD (Corder et al., 1993). We have shown that an increase in expression of APOE is associated with AD in LPS induced monocytes (2 hours) but this is not evident in monocytes induced with LPS for 24 hours. However, the same eQTL and direction of change expression is seen in GTEx lung tissue. The most significantly associated eQTL SNP, rs5157 is an intron variant of APOC4 that is located in a regulatory region upstream of the APOC2 gene.

BIN1 We have shown that a decrease in expression of BIN1 is associated with AD in LPS induced monocytes (2 and 24 hours), but not in naive CD14+ or in IFN-induced monocytes. The most significantly associated eQTL SNP, rs6710467 is an intergenic variant upstream of BIN1 that has been associated with acute myeloid leukaemia (Lv et al., 2017). A decrease in expression of this gene is also associated with AD in ten of the GTEx7 tissues, using TWAS, but only two of these are AD-relevant; Brain Cerebellum and Brain Cerebellar Hemisphere. We note that previously published eQTL studies show similar results to our TWAS analysis for the association between a change in expression in BIN1 and rs6710467 in monocytes (Fairfax et al., 2012), whole blood and cerebellum (Kunkle et al., 2019).

MS4A locus The MS4A region is a genome-wide significant AD risk locus. Multiple genes in this locus are in high linkage disequilibrium (LD). After conditional analysis, we detected an association between an increase in expression of MS4A4A in naive CD14+ monocytes and AD. The association between and increase in expression of MS4A4A and AD has been shown in GTEx7 whole blood (rs573122) and thyroid (rs600550), (Supplementary Material Table 4 ) and (Kunkle et al., 2019). In contrast, in the LPS induced monocytes (2 and 24 hours) we identified a statistically significant decrease in MS4A4E expression in AD. We did not detect any association between changes in expression of genes at this locus and AD in IFN-induced monocytes. Using TWAS, we did not detect an association between changes in expression of MS4A6E and AD in any of the GTEx tissues, YFS or NTR blood, which contradicts a previous report of an eQTL effect (an increase in expression) in whole blood (Zhernakova et al., 2017). However, the decrease in gene expression associated with AD that we identified at the MS4A locus using TWAS may be specific to LPS - induced monocytes.

The most significantly associated eQTL SNP in the MS4A2 locus in naive monocytes was rs6591559 which has been reported previously as an eQTL in monocytes (Zeller et al., 2010) This SNP is upstream of MS4A4A in the intergenic region between the MS4A4A and MS4A4E In LPS-induced monocytes the most significantly associated eQTL SNP is rs11824734, which was a downstream transcript variant of MS4A4A. Both of the SNPs in this locus are in regulatory regions, but they are not in a known transcription factor binding site.

PTK2B We show that there is AD- associated increase in expression of PTK2B in CD14+ monocytes, whole blood and peripheral blood (GTEx7 and YFS respectively) whereas there is an AD- associated decrease in expression LPS-induced monocytes (24 hours). This association is not seen in other GTEx tissues, for example in Brain Cerebellum suggesting that the association of this gene with AD is specific to blood. In this TWAS analysis, the most significantly associated eQTL SNP, rs17057043 in CD14+ naive monocytes, peripheral (NTR) and whole (YFS) blood and in LPS-induced monocytes is located in intron 5 of PTK2B. Previously this SNP has been reported to affect the binding of IRF1, a transcription factor that regulates the innate and acquired immune response and it is involved in some of the cytokine responses to LPS (Rosenthal et al., 2014). Interestingly, this eQTL shows cell-specific opposite directional effects between naive monocytes and LPS induced monocytes.

PVR PVR /CD155 was first identified as the receptor for polio virus, but it has been shown to have many biological roles (Bowers et al., 2017). It is important in the immune response, regulating cell-mediated immunity by promoting monocyte trans-endothelial migration (TEM) (Reymond et al., 2004). PVR has been associated with AD in an AD-by-proxy meta- analysis (Marioni et al., 2018). We have shown that a decrease in expression of PVR is associated with AD specifically in LPS - induced monocytes (24 hours), several GTEx tissues including subcutaneous adipose, but not in brain tissues or whole blood. The eQTL SNP, rs10426401 is in a regulatory region in the first intron of PVR and could affect several transcription-factor binding sites.

SPI1 In all four monocyte cell strains tested, we detected an association between an increase in expression of SPI1 and AD. These associations were not seen in whole blood or peripheral blood, they are specific to monocytes. In naive CD14+ cells, IFN and LPS24 induced cells, the most significantly associated eQTL SNP was rs10838698. This SNP has been reported previously as a candidate variant affecting SPI1 gene expression (Huang et al., 2017). However, the intronic variant, rs755553 is the most significantly associated eQTL SNP in LPS2 cells in this analysis. This SNP is in a regulatory region of the SLC39A13 gene.

Supplementary Figures

Supplementary Fig 1. Genes for which cis-heritable expression was computed overlap between naive and induced monocyte cell types. UpSet plots show the numbers of genes in common and unique to each of the monocyte cell types: Naive CD14+ cells (CD14), CD14+ cells induced with LPS for 2 hours (LPS2), CD14+ cells induced with LPS for 24 hours (LPS24) and IFN-induced CD14+ cells (IFN).

A CD14 v LPS2 B CD14 v LPS24 CD14

R = 0.77 R = 0.75 LPS2

LPS24

BOTH

C CD14 v IFN D LPS2 v LPS24 R = 0.83 R = 0.83

Supplementary Fig 2. Correlation plots of Z-scores from TWAS in monocytes. Genes are colour-coded according to their TWAS significance in cells each monocyte lineage: naive CD14 = purple, LPS2-induced =orange, LPS24_induced =green, or in both cell types (blue). The increase in expression of SPI1 associated with AD is present in all of the monocyte lineages and that of LACTB2 in naive CD14, LPS24 induced and IFN induced cells. R denotes the Pearson correlation co-efficient between the Z-scores in each case.

Monocyte A CD14 B LPS2 YFS blood R = 0.72 R = 0.46 Both

C LPS24 D IFN R = 0.58 R = 0.62

Supplementary Fig 3. Correlation plots of Z-scores from TWAS in monocytes and YFS blood. Genes are colour-coded according to their TWAS significance in monocyte lineages (purple), YFS blood (orange) or in both cell types (blue). R denotes the Pearson correlation co-efficient between the Z-scores in each case.

A CD14 B LPS2 Monocyte NTR blood R = 0.62 R =0.32 Both

C LPS24 D IFN

R = 0.41 R = 0.44

Supplementary Fig 4. Correlation plots of Z-scores from TWAS in monocytes and NTR blood. Genes are colour-coded according to their TWAS significance in monocytes (purple,) NTR blood (orange) or in both cell types (blue). R denotes the Pearson correlation co- efficient between the Z-scores in each case.

A CD14 B LPS2 Monocyte

CMC R = 0.37 R = 0.36 Both

C LPS24 D IFN

R = 0.35 R = 0.33

Supplementary Fig 5. Correlation plots of Z-scores from TWAS in monocytes and CMC dorsolateral pre-fontal cortex (DLPFC). Genes are colour-coded according to their TWAS significance in monocytes (purple), CMC - DLPFC (orange) or in both cell types (blue). R denotes the correlation co-efficient between the Z-scores in each case. R denotes the Pearson correlation co-efficient between the Z-scores in each case.

A CD14 B IFN Marioni R = 0.23 R = 0.18 Kunkle

Both

LPS2 LPS24 C R = 0.23 D R = 0.2

Supplementary Fig 6. Correlation plots of Z-scores from TWAS using Kunkle and Marioni summary statistics. TWAS significant genes (after Bonferroni correction) are colour-coded according to their being in the Kunkle (orange), Marioni (purple) or both (blue) summary statistics. The TWAS results for the PTK2B, MS4A6E and PVR genes are replicated in the Marioni TWAS in CD14+, LPS2 and LPS24 cells respectively. R denotes the Pearson correlation co-efficient between the Z-scores in each case.

Supplementary Tables.

No. of TWAS No. of TWAS significant genes No. of TWAS No. of Genes with cis- Monocyte significant genes in Kunkle TWAS that survive significant genes heritable expression in Kunkle conditional analysis replicated in Marioni * CD14 1668 7 4 1 LPS2 1559 6 5 1 LPS24 1579 6 6 1 IFN 1807 2 2 0

No. of genes with significant TWAS association after Bonferroni correction *Marioni summary statistics = UK Biobank GWAS on parental AD - meta analysis of log-odds and SEs from maternal and paternal AD (Marioni et al., 2018)

Supplementary Table 1. Summary of TWAS significant genes in the Kunkle and Marioni analysis for each monocyte cell type. Genes with cis-heritable expression were used in the TWAS analysis for each cell type using Kunkle (Kunkle et al., 2019) and Marioni (Marioni et al., 2018) summary statistics. Three TWAS significant genes derived using the Kunkle summary statistics were replicated in the TWAS analysis using Marioni summary statistics: PTK2B, PVR, MS4A6E. The numbers of TWAS significant genes in each monocyte cell type obtained using the Kunkle summary statistics before and after conditional analysis are shown.

Supplementary Table 2 (excel sheet ST2). Results of TWAS analysis from monocytes. TWAS results using Kunkle summary statistics ((Kunkle et al., 2019)) and expression weights derived from monocytes: Naive CD14+ cells (CD14), CD14+ cells induced with LPS for 2 hours (LPS2), CD14+ cells induced with LPS for 24 hours (LPS24) and IFN- induced CD14+ cells (IFN).

GENE/CELL CD14 LPS2 LPS24 IFN TYPE APOE BIN1 FNBP4 LACTB2 MS4A4A MS4A6A MS4A6E MYBPC3 PLIN2 PTK2B PVR SPI1 STX3

Supplementary Table 3. TWAS significant genes across the four monocyte cell types for which cis-heritable expression was computed. : denotes that a gene was present in the computed expression weights for a given cell type. : denotes that a gene was TWAS significant in the given cell type.

GENE Chromosome Locus Conditional Cell type Known in AD GWAS analysis BIN1 2 LPS2, LPS24 (Seshadri et al., 2010) PTK2B 8 CD14, (Lambert et al., 2013; LPS24 Kunkle et al., 2019) LACTB2* 8 CD14, LPS24, IFN PLIN2* 9 LPS2 SPI1 11 CELF1 CD14, LPS2, (Huang et al., 2017) LPS24, IFN FNBP4 11 CELF1 dropped LPS2 (Karch et al., 2016) MYBPC3 11 CELF1 dropped CD14 (Huang et al., 2017; Katsumata et al., 2019) MS4A4A 11 MS4A CD14 (Naj et al., 2011) MS4A6E 11 MS4A LPS2, LPS24 (Naj et al., 2011; Karch et al., 2016) MS4A6A 11 MS4A dropped CD14 (Hollingworth et al., 2011; Jansen et al., 2019) STX3 11 dropped CD14 APOE 19 APOE LPS2 (Farrer et al., 1997) PVR 19 APOE LPS24 (Marioni et al., 2018)

Supplementary Table 4. Summary of the TWAS significant genes across the four monocyte cell types. 13 genes were TWAS-significant across the four monocyte cell strains: Naive CD14+ cells (CD14), CD14+ cells induced with LPS for 2 hours (LPS2), CD14+ cells induced with LPS for 24 hours (LPS24) and IFN-induced CD14+ cells (IFN). After conditional analyses we identified 9 genes with statistically independent TWAS signals (shown in bold), two of these, LACTB2 and PLIN2 are novel candidate genes for AD (shown with *).

Supplementary Table 5 (excel sheet ST5). Results of TWAS analysis from 52 tissues. TWAS results using Kunkle summary statistics (Kunkle et al., 2019) and expression weights derived from GTEx7 tissues, CMC. BRAIN (DLPFC), METSIM.ADIPOSE, YFS.BLOOD and NTR.BLOOD.

Supplementary Table 6 (excel sheet ST6). Correlation of TWAS Z-scores between monocyte cell strains and AD-relevant tissues. Correlation co-efficients (R2) and corresponding p-values for the correlation between the TWAS Z-scores using Kunkle summary statistics for each monocyte cell strain and relevant AD tissues: GTEx7 Brain, CMC_Brain (DLPFC) and GTEx7 whole Blood, NTR.BLOOD, YFS.BLOOD, GTEx7 Adipose and METSIM.ADIPOSE. the no. of genes in the overlap of the two variables is shown in each case.

CELL_TYPE GENE CHR GENE_START GENE_END K_TWAS.Z K_TWAS.P YFS.BLOOD BIN1 2 127805603 127864931 4.15 3.27E-05 NTR.BLOOD BIN1 2 127805603 127864931 3.83 1.26E-04 GTEx7_Whole_Blood BIN1 2 127805603 127864931 1.09 2.76E-01 YFS.BLOOD FNBP4 11 47738072 47788995 -5.62 1.88E-08 GTEx7_Whole_Blood FNBP4 11 47738072 47788995 -4.60 4.31E-06 YFS.BLOOD LACTB2 8 71547553 71581409 4.32 1.53E-05 NTR.BLOOD LACTB2 8 71547553 71581409 -2.87 4.12E-03 GTEx7_Whole_Blood LACTB2 8 71547553 71581409 -1.56 1.19E-01 CMC.BRAIN LACTB2 8 71547553 71581409 0.86 3.92E-01 YFS.BLOOD MS4A6A 11 59939081 59952139 7.37 1.73E-13 NTR.BLOOD MS4A6A 11 59939081 59952139 6.77 1.29E-11 GTEx7_Whole_Blood MS4A6A 11 59939081 59952139 6.55 5.93E-11 GTEx7_Whole_Blood MYBPC3 11 47352957 47374253 3.29 9.97E-04 YFS.BLOOD PLIN2 9 19108373 19149288 -1.51 1.30E-01 NTR.BLOOD PLIN2 9 19108373 19149288 -2.36 1.82E-02 YFS.BLOOD PTK2B 8 27168999 27316903 5.05 4.33E-07 NTR.BLOOD PTK2B 8 27168999 27316903 5.90 3.74E-09 GTEx7_Whole_Blood PTK2B 8 27168999 27316903 4.95 7.30E-07 GTEx7_Whole_Blood PVR 19 45147098 45166850 -3.93 8.54E-05 CMC.BRAIN PVR 19 45147098 45166850 -5.98 2.19E-09 YFS.BLOOD SPI1 11 47376411 47400127 3.88 1.06E-04 YFS.BLOOD STX3 11 59480929 59573354 -0.80 4.23E-01

Supplementary Table 7. Transcriptome-wide association study (TWAS) test statistics for genes in NTR blood, YFS blood and GTEx Whole blood and CMC brain (DLPFC) that were TWAS-significant in monocytes. K_TWAS.Z denotes the gene-level TWAS Z-score and K_TWAS.P denotes the TWAS p-value using the Kunkle 2019 summary statistics (Kunkle et al., 2019). TWAS significant genes after multiple testing correction (Bonferroni) are shown in bold.

Conditional analysis plots

Manhattan plots of the Kunkle 2019 GWAS data before (grey) and after (blue) conditioning on the green genes. SNPS are represented by coloured points plotted on the x axis by genomic location. The genes in the locus are represented at the top of the plot. Blue genes are marginally TWAS associated genes and green genes are jointly significant genes. The monocyte cell strain in which genes in the locus were TWAS-significant are shown in each plot.

1. Locus: PTK2B Monocyte cell strain: CD14, LPS24:

PBK SCARA3 SCARA5 EPHX2 CCDC25 PTK2B MIR6843 ESCO2 TRIM35 CHRNA2 MIR3622A NUGGC ADRA1A STMN4 MIR6842 CLUMIR3622B MIR4287

●● ● 15 ●●●

10 ● ●

●

● ●

● ● ● ● ● ●● ● ● ● ●● 5 ● ● ● ● ●● ● ● ● ●●●● ● ● ● ●●● ● ● ● ● ● ● ●● ●● ● ● − log10(P value) ● ● ●● ● ● ● ●● ● ● ● ●●● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ●● ●● ●● ● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ●●● ●●●● ● ● ● ● ●●●●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ●●● ● ● ● ●● ●● ●●● ●● ● ●●●● ●● ● ● ● ● ● ● ●● ● ●● ● ●●● ● ● ● ● ● ●●● ●● ●● ● ●●● ●● ● ● ●● ● ●● ●● ● ●● ● ● ● ● ●●●●●● ●●● ● ● ● ● ●●● ● ●● ●●● ●● ●● ● ● ● ● ●●●● ●●●●●●● ● ● ● ● ● ● ● ● ●● ●● ●● ● ●● ● ● ● ● ●●● ●● ● ● ●●●●●●●●●●●● ● ● ● ●● ●●●●●● ● ●●● ● ●● ●● ●●● ● ● ● ● ●● ● ● ●● ● ● ● ● ●● ●● ● ● ●●●● ●● ● ●● ●● ●● ● ● ●● ● ●●●●● ●●● ● ●●● ●●●●● ● ●● ● ●●● ● ●● ●●●●● ● ● ● ●● ● ●●● ●● ●● ●● ●●● ●●●●●●● ● ● ●● ●●●● ● ● ● ● ● ● ● ●● ● ● ●●● ● ● ●● ●● ● ● ● ●●●●●●●●●●● ●● ● ●● ● ●● ●● ●● ● ● ●● ●● ● ● ●●● ●●●●● ● ● ● ●● ● ●● ●●● ●●● ●●● ●●● ●●●●● ●● ●●● ●●●●●● ● ● ● ● ●● ● ● ●● ●●●●●● ●● ●●●● ● ●●● ● ●●●●●● ● ● ● ● ● ●● ● ● ● ● ●●●●●● ●●●●●●●●●●● ● ●● ● ●●●●● ●● ●● ● ●●●● ● ●●●● ●●●● ● ●● ● ● ● ● ●●● ●●●● ● ● ●● ● ● ● ●● ● ● ● ● ●● ● ● ● ●● ●●●● ● ● ● ●● ● ● ●● ● ● ● ●●● ● ● ●●● ●●● ●●●● ●●●●●●●● ●● ● ● ● ●●●● ●●●● ● ●●● ●●● ●● ● ●● ●●●●●●● ●● ●●●●● ●● ●●●●●● ●● ● ● ●● ● ●●● ●●●● ●● ● ●●●●●●●●●●●●●●●●●●●●● ● ●● ●●● ● ●●●●● ●● ●●●● ●●●●●● ● ● ● ● ●●●● ●● ● ● ●●●●●● ● ● ● ● ●● ●● ● ●● ●●● ● ● ● ●●● ●● ● ●● ●●●●●●●●●● ●●● ● ●● ● ● ● ●● ●● ●●●●●●●●●●●●●●●● ● ●●●●● ●● ●●●●●●●●●●●●●●●●●●●● ●●●● ●●●●●●●●●●●●●●●● ●●●●●● ● 0 ●●●●●●●●● ●●●●● ●●●● ●● ●●●●●●● ●●●●●●●●●●●●●● ● ● ● ● ● ●●● ●●●●●●● ●●●●●●●● ● ●●●● ● ● ● ● ● ●● ● ●●●●●● ●● ● ● ● ●● ●●●●●●●● ● ● ●●● ● ●●●●●●●●●● ●●●●●●●●●●●●●● ●●●● ●●●● ● ●● ●●● ● ● ● ● ●●●● ●● ●●●●●●●● ●●●●●● ● ●● ●● ● ● ●●●●●●●●●●●●●●●●●●●●●●● ● ● ● ● ●●● ●● ●●●●●●●

26.6 26.8 27.0 27.2 27.4 27.6 27.8

chr 8 physical position (MB)

2. Locus: LACTB2 Monocyte cell strain: CD14, IFN, LPS24:

XKR9 LOC286190 LACTB2 NCOA2 TRAM1 PRDM14 LOC101926892 EYA1

● ● ● ●● ● ● ● ● ● ● ● ● ● 5 ●

● ● ● ●● 4 ●

● ● 3 ●

● ●● ● ● 2 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ●●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ●●● ● ● ● ● ● − log10(P value) ● ● ● ● ● ● ● ● 1 ●● ● ● ●● ● ● ● ● ●● ●● ● ● ●●● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ●●●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ●●● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ●● ●●● ●●●●● ● ● ● ●● ●● ● ● ● ● ● ● ●● ●●● ● ● ●●● ●● ● ●● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ●● ● ●●● ●● ●●●●● ● ●● ●● ●●● ● ● ● ●● ● ●● ● ●●● ● ●●●●● ● ● ●●● ●● ● ●● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ●●● ●● ●● ●● ● ● ● ● ● ● ●●● ●● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ● ●● ●● ●● ● ●● ●● ● ● ●● ●●● ●●● ●● ● ● ●●● ●● ● ● ● ●●●●● ● ● ● ● ●● ● ●●●●● ● ●● ●● ● ● ● ● ●●● ● ● ● ● ● ● ●●●● ● ●●●●● ● ●●●● ● ● ● ●● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ●●● ●● ● ●● ● ● ●●●●● ● ● ●● ●● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●●●● ●● ● ● ● 0 ● ●●● ● ● ● ●● ●● ● ●● ● ● ● ● ● ● ● ● ●● ● ●●●●● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ●●●● ● ●● ● ● ● ●●●●● ●●●●●● ● ●● ●● ●

71.0 71.2 71.4 71.6 71.8 72.0 72.2

chr 8 physical position (MB)

3. Locus: SPI1 Monocyte cell strain: CD14, IFN, LPS2, LPS24:

MADD NR1H3 MTCH2 ACP2 C1QTNF4 LRP4 DDB2 RAPSN NDUFS3 LRP4−AS1 MIR6745 PSMC3 KBTBD4 SNORD67 PACSIN3 SLC39A13 FAM180B NUP160 MIR5582 C11orf49 SPI1 CELF1 AGBL2 CKAP5 ARFGAP2 MYBPC3 PTPMT1 FNBP4

●●● ● ● ● ●● ● ●

●● ● ● ● ● ● 8 ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ●● ● ● ●

● ● 6 ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ●● ● 4 ● ● ●● ● ●● ● ●● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● − log10(P value) ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●●●● ● ● ● ● 2 ● ● ● ●● ● ●● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●● ●● ● ● ●● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ●● ●● ● ● ●●●● ●● ● ● ●● ●●● ● ● ● ● ● ●● ● ● ●●● ●● ● ●● ●●● ●● ●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●●● ● ●●● ● ● ●●● ● ●●● ●● ● ● ●● ●● ● ● ● ●●● ● ● ● ● ● ●● ● ● ●● ●● ● ●●● ● ●●● ●●● ●●● ● ●●● ●●● ● ● ● ●●● ● ●● ●● ●● ●● ● ● ● ● ● ● ● ●● ● ● ● ● ● ●● ●●● ● ● ●● ● ●● ● ● ● ●● ●● ● ●● ●● 0 ● ● ●● ● ●●● ● ●●● ●●●●● ●●●●●● ●● ● ●● ● ●● ●● ● ● ● ●●● ●●● ● ●● ●●●● ●●●● ●●●●●●●●●●●● ● ●●●● ●●● ●●●● ●● ●●●● ● ●●● ● ●● ● ●● ● ●●●●●●●●●●● ●● ● ●● ●●●●●●● ● ● ●● ●●●●● ●●●● ● ● ● ●

46.8 47.0 47.2 47.4 47.6 47.8 48.0

chr 11 physical position (MB)

4. Locus: MS4A4A Monocyte cell strain: CD14

MS4A12 OR4D9 MS4A5 ZP1 OR4D10 OR10V2P MS4A14 PTGDR2 MPEG1 OR4D6 STX3 MS4A7 CCDC86 DTX4 OR5A1 PATL1 TCN1 MS4A6A MS4A1 MS4A10 FAM111A OR5A2 MIR3162 GIF MS4A2 MS4A6E MS4A8 PRPF19 LOC101927204 OR4D11 OR10V1 MS4A3 MIR6503 MS4A13 MS4A15 FAM111B OR5AN1 OSBP MRPL16 OOSP2 MS4A4A LINC00301

● ●● 15 ● ●● ● ● ●● ● ● ● ● ● ●● ● ●

● ● ●● ●●

● ● ● ● ● ● 10 ● ●● ● ●

● ● ●● ●● ● ●● ●● ●●●● ● ● ●● ●● ● ● ● ● ●● ● ● ● ● ● ●● 5 ●● ● ● ● ● ● ● ● ● ● ● ● ● − log10(P value) ● ● ● ●● ●●●● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ● ●● ● ●● ● ●● ● ● ●● ● ● ● ● ●● ● ●● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ●● ● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ●●● ● ●● ● ● ● ● ● ● ● ● ● ● ●●● ●●●●● ● ● ● ● ● ● ● ● ●●●● ● ● ● ● ● ● ● ● ● ●●● ● ●● ● ●● ● ● ● ●●●●●●● ● ●● ●● ● ●● ●● ●● ● ●●●●● ● ● ● ●● ● ● ● ●●●●● ● ●●● ●●● ●●● ● ● ● ● ●●● ● ●● ● ● ● ● ●● ●● ● ● ●●● ● ● ●●● ● ● ● ● ● ● ● ● ●● ● ●● ●● ● ● ●●● ●●● ● ● ● ● ● ● ●● ●● ● ●●● ●●● ● ●● ● ●●●● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ● ●●●● ● ● ●●● ●● ● ●● ●● ● ●●● ● ●●●● ●●●● ●● ● ● ● ● ●●● ●● ●●●●●● ●●●●●● ●●●● ● ● ●●● ●● ●● ● ● ● ●●● ●● ● ●●● ●●● ● ●●●●● ● ●● ● ●●● ● ● ●● ●● ●●●● ● ●●●● ●●● ● ● ●●●● ●●● ●● ● ●●●●● ● ●●●● ●●●●● ● ●● ● ●●● ●● ●●●●●●● ● ● ●● ●●● ●●● ● ● ● ● ● ●● ●●●● ●●●●●●● ●● ● ●●● ● ●● ●● ●● ●●●●●● ●●●●●● ●● ●● ●●●●● ●● ●●●● ● ● ●●●●●●●●● ●●●●●●● ● ● ● ●●● ● ● ●●●● ●●●●● ● ●●●● ● ● ● ●●●●● ●● ●● ●●●● ●●●●●●●● ●●●●●●● ●● ●● ● ● ● ●●●● ● ●●● ● ● ●●●●● ●●●●●●●●●●● ●●● ●● ● ● ● ●●● ●● ●●● ● ●● ● ● ●●●● ● ●● ●●● ●● ●●● ● ● ● ● ● ● ●●●● ●●●●● ●● ● ● ●●● ●● ●●● ●●● ● ● ● ●● ●● ● ●●●●●●●● ● ● ● ● ● ● ●● ● ● ●●●●●● ●●● ●● ●●● ● ● ● ● ●●●●●● ●● ● ● ● ●● ● ●● ● ● ● ●● ●●●●●●●● ●●●●●●●●● ● ●●●● ● ● ●●●●● ●●●● ●●●●● ●● ●● ● ●●●● ●● ●●●●● ●● ● ● ● ● 0 ● ● ●●●●●●●● ● ●●●● ●●● ● ● ●● ●● ●● ●●●●●● ●● ● ● ● ●●● ●●●●● ●● ● ●●●●●● ● ●● ●●●●●●●●●● ●● ●●●●●●●●●● ●●● ●● ●●● ●●●●●● ●●●●●●●●●● ● ●●●●●●●●● ●● ●●●●●● ● ●● ●●●●●● ●● ● ●● ●●● ●●●● ●●● ●●●●● ●●● ●●●●

59.0 59.5 60.0 60.5

chr 11 physical position (MB)

5. Locus: BIN1 Monocyte cell strain: LPS2, LPS24

WDR33 MAP3K2 SFT2D3 ERCC3 IWS1 GPR17 BIN1 MIR4783 LIMS2 GYPC CYP27C1 PROC MYO7B

20 ●

● 15

●● ● ● 10 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 5 ● ●

− log10(P value) ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ● ●● ● ●● ●● ● ● ●●● ●● ●● ● ●● ● ●●● ●● ●●● ●● ● ● ● ●●● ● ●● ● ●● ● ●●● ●● ● ● ●●●●● ●●●● ● ●●●● ● ● ● ● ●●● ● ●● ● ●●● ●●● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●●● ● ● ● ● ●● ● ●● ● ● ● ● ●● ● ● ● ● ●● ●● ●● ● ●●● ●● ●● ● ● ●● ● ●●●● ●● ● ● ● ●● ● ● ●●● ● ● ● ● ●● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ●●● ● ● ●●●● ● ●●●●● ● ●● ● ● ● ●● ● ● ●● ● ●● ● ● ●● ●●● ● ●●● ● ● ● ● ● ● ● ●● ● ●●●● ● ●●●●● ● ● ● ●●● ● ●● ● ●●● ●●●● ●● ● ●●● ●● ●●● ● ●●●●●● ● ●●●●●● ●● ●●● ●● ●●●● ● ●●●● ●●● ●● ●●● ●●●●●●●●●● ● ● ●● ● ● ●● ● ● ●●●●● ●●● ●●● ● ● ●● ●●●● ● ● ● ●● ●●● ● ●●● ● ●●● ●●● ●●●●● ●●● ●●●●●●●●●●● ●●●●●●● ●●● ●●●●● ●●●● ● ●●● ● ●●●●●●●● ●●●●●●●●●●● ● ● ● ● ●●●●● ●●● ●●●● ● ●● ●●● ● ● ●●●●● ●●●●●● ●●● ●● ● ●●● ●● ●●●●●●● ●●● ● ●●●●● ● ●●● ● ●●● ● ●● ●●● ●●●●●● ●●●●●●●●●●● ●● ● ●●●●●●●●●●● ● ● ●● 0 ●●●● ● ●●● ●● ●● ● ● ●●●● ●●●●●●●●●●● ●●●● ●●●●●●●●●●●●●●●●●●●●●● ●● ●●●●● ●●●●●●●●●● ●●● ●●● ●●●● ●●● ● ●●●●●●● ●● ●● ● ●● ●●●● ●●●●●●●●●● ●● ● ● ●●●●● ● ● ●●●●● ●●●●●●● ● ● ● ●● ●● ●●● ●●● ●● ●●●●●●●●●●●●●●●●● ● ●●●●●● ● ● ●●● ●●●●●●● ● ● ●●

127.2 127.4 127.6 127.8 128.0 128.2 128.4

chr 2 physical position (MB)

6. Locus: PLIN1 Monocyte cell strain: LPS2

SCARNA8 HAUS6 RRAGA ACER2 MIR3152 FAM154A RPS6 SLC24A2 ADAMTSL1 PLIN2 DENND4C

● ●

● 3.0 ● ● ● ●● 2.5 ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● 2.0 ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ● 1.5 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ●● ● ● 1.0 ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●●● ●● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ●● ●● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ●● ● ● ● ●● ● ●● ● ● ● ● ● ●● ●●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ●● ● ● ●● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ●●● ●● ●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ● ● ● ● ● ●●● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●● ● ● − log10(P value) ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ● ●● ●●● ● ● ● ● ●● ● ●● ● ●● ● ● ● ●● ● ● ● ● ● ● ●●● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ●● ● ● ●● ● ● ● ● ● ●● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ● ●● ● ● ● ●● ● ● ● ●●● ● ● ●● ●● ●● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ●●● ● ● ● ●● ● ● ● ● ●● ● ● ● ● ● ●● ● ●● ● ● ● ●● ●●● ●● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●●● ● 0.5 ● ● ● ● ● ●●● ● ● ● ● ● ● ● ● ●● ● ●● ●●●● ●●●●● ●●● ● ● ● ● ●●●● ● ● ● ● ● ●● ● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ●● ●● ●● ● ● ● ● ●● ● ●● ● ●●● ●●● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ●● ●●● ● ● ● ● ● ● ●● ● ●●● ●●●● ● ● ●● ● ● ●●● ● ● ● ●● ●●●● ● ● ● ●●● ● ● ● ●● ● ● ● ● ●● ●● ●● ● ●● ● ●● ● ● ● ●● ● ● ●● ● ● ● ●● ●●●● ● ● ●●● ●● ●●●● ● ●● ● ●● ● ●● ● ●● ● ● ●● ● ●●●● ● ● ●● ● ● ● ● ● ●● ●● ● ● ● ●● ●●● ● ● ● ● ● ● ● ● ●●●●● ●● ● ●●● ● ●● ●●● ● ●●●● ●●●● ● ● ●● ●● ●●●● ●● ●● ● ● ●●● ● ● ●● ● ●● ● ● ●●●● ●● ● ● ● ● ●● ● ● ● ● ● ●●● ● ● ●● ● ●●● ● ● ● ● ● ●●●● ●●●● ●● ● ●● ●●●●● ●● ●●●● ●●●● ● ● ●●●● ● ● ●●●● ●● ●● ● ● ● ●● ● ● ●● ● ● ● ● ● ● ●●● ● ● ● ●● ● ● ●●●●● ●● ●● ● ●● ●● ●● ● ● ● ● ●●●● ● ● ● ●●● ●● ●●● ●● ● ● ● ● ●●● ●● ● ●●● ●●●●●● ●●● ●● ● ● ● ● ● ● ●● ● ● ●● ● ● ● ● ●● ● ● ● ●● ● ● ● ● ●● ●● ●●● ● ●●●● ●● ● ● ● ●●● ● ● ●● ● ● ●● ● ● ● ● ● ●●●●●● ●● ●●● ●●●●● ●●●●● ●● ●●●●●●● ●●● ●●●●● ●●●●● ●●●● ● ● ● ● ● ●● ●● ● ● ● ● ● ● ●●● ● ●●● ● ● ● ● ● ● ●●● ● ●●●● ●●● 0.0 ● ● ● ●●● ●●● ●●●● ●● ● ● ● ●● ●● ●● ●● ●●● ● ●●●● ●●●● ●●●●●●● ●●●●● ●● ● ● ● ● ● ● ●●● ● ● ● ● ● ● ● ●● ● ●●● ●●● ● ● ●●●●●● ● ● ●●●● ●●

18.6 18.8 19.0 19.2 19.4 19.6

chr 9 physical position (MB)

7. Monocyte cell strain: LPS2, LPS24 Locus: MS4A6E

SLC15A3 TMEM132A MS4A5 ZP1 TCN1 MS4A14 PTGDR2 GIF MS4A7 MS4A13 MS4A10 CD6 MRPL16 MS4A2 MIR6503 MS4A12 MS4A15 TMEM109 STX3 MS4A3 MS4A4A MS4A1 MS4A8 CCDC86 OR10V2P OOSP2 MS4A6A MS4A6E LINC00301 PRPF19

● ● 15 ● ●● ● ●● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●

● ●● ● ● ● ● ●● ● 10 ●

● ● ●● ● ● ● ●● ●● ●●●●● ● ● ●● ●● ● ● ● ● ●● ● ●

5 ● ● ●

− log10(P value) ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ●●● ● ● ●●● ● ● ● ●● ●● ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●●●● ● ●● ● ● ● ● ● ●● ● ●● ●● ● ● ● ● ● ● ●●●● ●● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ●● ● ●● ●●●●●●●● ● ●●● ● ● ● ● ●● ● ● ●●●● ● ●● ● ●● ● ● ● ● ●● ● ● ● ● ● ● ● ● ●●●●●● ●●● ● ● ●●● ● ● ● ● ● ● ● ● ●● ● ●● ●● ● ●● ● ● ● ● ●● ● ● ● ● ●●● ● ● ●●●●● ●● ●● ● ● ●●● ●●●●● ● ● ●● ● ● ● ●● ●● ● ●●●●●●●●●●● ●●● ●●● ● ● ● ● ● ● ●●● ●● ● ●● ● ● ● ● ● ● ● ●●●●● ● ● ●● ● ● ● ●●●●●●●● ● ● ●●● ●● ●●● ● ● ● ●● ● ● ●●●●● ● ●●●● ●●●●● ● ● ● ●● ● ●●●● ●● ● ● ●●●● ●●●● ● ● ● ● ● ●●● ● ● ●●●●●● ● ●● ●●● ●● ● ● ● ● ● ● ● ●●●●●● ●● ●●● ●●●●● ● ● ●● ● ●●●● ● ● ●● ●●● ●●●●●●● ● ●●●●● ●●● ●●● ●●● ● ● ● ● ●●● ● ● ● ●● ● ● ● ●●● ●● ● ●●●● ● ●●● ● ● ● ●● ● ●●● ●●●● ●● ●● ● ● ● ●● ●●● ● ●●● ● ●● ●●● ● ●●●●● ● ●●● ●●● ● ●● ● ●● ●●● ●●●●● ●●●● ●●●●● ● ●●●● ● ● ● ● ●●●●●● ●●● ●● ●●●● ● ● ●● ● ● ● ● ●●● ●●●●●● ●● ●● ● ● ●●● ●●● ●●●● 0 ●●●●●●●●●●●● ●●●● ●●● ●● ● ● ● ●● ●● ●● ● ● ● ●● ●● ●● ●● ●● ● ●●● ●● ●●●●● ●●●● ●● ●●●●●●●●●●●● ●●●● ●●● ●●●● ● ●●●● ● ●● ● ●●●● ●●● ● ● ●● ● ●● ●● ●● ● ●● ●●● ●● ●● ●●●● ●● ●● ● ●●● ●●●●●●●●●● ●●●●●●● ● ● ●●●●●

59.6 59.8 60.0 60.2 60.4 60.6 60.8

chr 11 physical position (MB)

8. Locus: APOE Monocyte cell strain: LPS2

CLPTM1 APOC2 BLOC1S3 CEACAM16 APOC4−APOC2 VASP CEACAM19 APOC4 TRAPPC6A PPP1R13L MIR4531 APOC1 GEMIN7 ERCC2 PPM1N ZNF180 PVR BCAM APOC1P1 PPP1R37 KLC3 RTN2 ZNF229 IGSF23 MIR8085 APOE CLASRP MARK4 FOSB ZNF285 CEACAM22P CBLC TOMM40 ZNF296 EXOC3L2 ERCC1 ZNF112 CEACAM20 BCL3 PVRL2 RELB NKPD1 CKM CD3EAP ●

● ●● 150 ●

●

● ● ● ● ● ● ● ● ● ● ● 100 ● ●

● ●

● ● ●●

●

● ● ● 50 ●

44.8 45.0 45.2 45.4 45.6 45.8 46.0

chr 19 physical position (MB)

9. Locus: PVR Monocyte cell strain: LPS24

CLPTM1 APOC2 BLOC1S3 ZNF226 CEACAM16 APOC4−APOC2 ZNF234 CEACAM19 APOC4 TRAPPC6A ZNF225 ZNF112 MIR4531 PVRL2 RELB NKPD1 LOC100379224 CEACAM20 BCAM APOC1P1 PPP1R37 ZNF224 ZNF235 ZNF180 PVR BCL3 TOMM40 GEMIN7 ZNF284 ZNF233 ZNF229 IGSF23 MIR8085 APOC1 ZNF296 MARK4 ZNF223 ZNF227 ZNF285 CEACAM22P CBLC APOE CLASRP EXOC3L2

● ● 150 ● ●

● ●● ● ●●● ● ● ● ● ● 100 ● ●

● ● ● ●● ● ● ●

● ● ● 50 ●

44.6 44.8 45.0 45.2 45.4 45.6 45.8

chr 19 physical position (MB)

Supplementary references.

Bowers JR, Readler JM, Sharma P, Excoffon KJDA. Poliovirus Receptor: More than a simple viral receptor. Virus Res 2017; 242: 1–6. Corder E, Saunders A, Strittmatter W, Schmechel D, Gaskell P, Small G, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science (80- ) 1993; 261: 921–923. Fairfax BP, Makino S, Radhakrishnan J, Plant K, Leslie S, Dilthey A, et al. Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles. Nat Genet 2012; 44: 502–10. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: A meta-analysis. J Am Med Assoc 1997; 278: 1349–1356. Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet 2011; 43: 429–436. Huang KL, Marcora E, Pimenova AA, Di Narzo AF, Kapoor M, Jin SC, et al. A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer’s disease. Nat Neurosci 2017; 20: 1052–1061. Jansen IE, Savage JE, Watanabe K, Bryois J, Williams DM, Steinberg S, et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat Genet 2019; 51: 404–413. Karch CM, Ezerskiy LA, Bertelsen S, Goate AM, Albert MS, Albin RL, et al. Alzheimer’s disease risk polymorphisms regulate gene expression in the ZCWPW1 and the CELF1 loci. PLoS One 2016; 11: e0148717. Katsumata Y, Nelson PT, Estus S, Fardo DW. Translating Alzheimer’s disease–associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs. Neurobiol Aging 2019; 74: 135–146. Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, et al. Genetic meta- analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet 2019 513 2019; 51: 414. Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, et al. Meta- analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 2013; 45: 1452–1458. Lv H, Zhang M, Shang Z, Li J, Zhang S, Lian D, et al. Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for Acute Myeloid Leukemia. Oncotarget 2017; 8: 7891–7899. Marioni RE, Visscher PM, Harris SE, Gale CR, Yang J, Zhang Q, et al. GWAS on family history of Alzheimer’s disease. Transl Psychiatry 2018; 8: 99. Naj AC, Jun G, Beecham GW, Wang LS, Vardarajan BN, Buros J, et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet 2011; 43: 436–443. Reymond N, Imbert A-M, Devilard E, Fabre S, Chabannon C, Xerri L, et al. DNAM-1 and PVR regulate monocyte migration through endothelial junctions. J Exp Med 2004; 199: 1331–41. Rosenthal SL, Barmada MM, Wang X, Demirci FY, Kamboh MI. Connecting the dots: Potential of data integration to identify regulatory snps in late-onset alzheimer’s disease GWAS findings. PLoS One 2014; 9: e95152. Seshadri S, Fitzpatrick AL, Ikram MA, DeStefano AL, Gudnason V, Boada M, et al. Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA - J Am Med Assoc 2010; 303: 1832–1840. Zeller T, Wild P, Szymczak S, Rotival M, Schillert A, Castagne R, et al. Genetics and beyond - the transcriptome of human monocytes and disease susceptibility. PLoS One 2010; 5: e10693. Zhernakova D V., Deelen P, Vermaat M, Van Iterson M, Van Galen M, Arindrarto W, et al. Identification of context-dependent expression quantitative trait loci in whole blood. Nat Genet 2017; 49: 139–145. URLs 1. https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-2232/. 2. Fairfax et al Supplementary Material: https://science.sciencemag.org/content/suppl/2014/03/05/343.6175.1246949.DC1?_ga=2.250 430726.142617004.1580743814-1392779675.1580743814 3. Illumina HumanHT-12_V4_0_R1_15002873_B array: https://www.ebi.ac.uk/arrayexpress/files/A-MEXP-2210/A-MEXP-2210.adf.txt 4. Biomart: https://bioconductor.org/packages/release/bioc/html/biomaRt.html 5. WGCNA: https://horvath.genetics.ucla.edu/html/CoexpressionNetwork/Rpackages/WGCNA/ 6. Liftover tool: https://genome.ucsc.edu/cgi-bin/hgLiftOver 7. Plink 1.9 http://www.cog-genomics.org/plink/1.9/ 8. LD Score Regression (LDSC) software : v1.0.0 : https://github.com/bulik/ldsc 9. HapMap 3 https://www.sanger.ac.uk/resources/downloads/human/hapmap3.html 10. Oliver Pain: OP_packaging_fusion_weights.R : https://github.com/opain/Calculating- FUSION-TWAS-weights-pipeline. 11. FUSION software http://gusevlab.org/projects/fusion/ 12. UpSetR: https://cran.r-project.org/web/packages/UpSetR 13. Common mind consortium: https://www.nimhgenetics.org/resources/commonmind