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Chunk #121 — Methods — GERA GWAS and MetaXcan Application

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Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics.
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European samples had been split into ten groups during imputation to ease the computational burden on the Michigan server, so after obtaining the imputed .vcf files, we used the software PLINK43 to convert the genotype files into the PLINK binary file format and merge the ten groups of samples together, while dropping any variants not found in all sample groups. For the association analysis, we performed a logistic regression using PLINK, and following QC practices from ref. 14 we filtered out individuals with genotype missingness >0.03 and filtered out variants with minor allele frequency <0.01, missingness >0.05, out of Hardy-Weinberg equilibrium significant at 1e-6, or had imputation quality <0.8. We used gender and the first ten genetic principal components as obtained from dbGaP as covariates. Following all filtering, our analysis included 61,444 European samples with 7,120,064 variants. MetaXcan was then applied to these GWAS results, using the 45 prediction models (GTEx and DGN).