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Chunk #94 — Methods — Expression model training

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Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics.
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To train our prediction models, we obtained genotype data and normalized gene expression data collected by the GTEx Project. We used 44 different tissues sampled by GTEx and thus generated 44 different tissue-wide models (dbGaP Accession phs000424.v6.p1). Sample sizes for different tissues range from 70 (Uterus) to 361 (Muscle—Skeletal). The models referenced in this paper make use of the GTEx Project’s V6p data, a patch to the version 6 data and makes use of improved gene-level annotation. We removed ambiguously stranded SNPs from genotype data, i.e., ref/alt pairs A/T, C/G, T/A, G/C. Genotype data was filtered to include only SNPs with MAF > 0.01. For each tissue, normalized gene expression data was adjusted for covariates such as gender, sequencing platform, the top three principal components from genotype data and top PEER Factors. The number of PEER Factors used was determined by sample size: 15 for n < 150, 30 for n between 150 and 250, and 35 for n > 250. Covariate data was provided by GTEx. For our analysis, we used protein-coding genes only.