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Chunk #64 — Methods — Polygenic Risk Scores

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Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations.
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To generate PRS from GWAS summary statistics in the MVP sample, we first conducted a GWAS for AUDIT-C and AUD as above, but restricted our analysis to two-thirds of the total sample by splitting the total sample randomly, keeping the number of AUD cases/controls balanced in each part (EA: N = 139,346, AA: N = 38,226). GWS loci identified from this analysis were the same as those in the larger sample, but were slightly decreased in significance. PRS were generated for the remaining EAs (N = 69,674) and AAs (N = 19,114) as the sum of all variants carried, weighted by the effect size of the variant in the GWAS. PRS were generated using PLINK2 (ref. 63). We performed p value informed clumping with a distance threshold of 250 kb and r2 = 0.1. Risk scores were calculated for a range of p value thresholds (P ≤ 1 × 10−7, 1 × 10−6, 1 × 10−5, 1 × 10−4, 1 × 10−3, 0.01, 0.05, 0.5, 1.0). PRS were standardized with mean = 0 and SD = 1. Logistic regression was