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Chunk #40 — Methods — AUD polygenic risk score in UKB.

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Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits.
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We calculated AUD polygenic risk scores (PRS) for each of the 82,930 unrelated subjects in UKB (application number 41910) who had non-missing AUDITP information [7]. A PRS was calculated as the sum of the number of effective alleles with pvalues less than a given threshold, weighted by the effect sizes from AUD meta-analysis (MVP+PGC). We analyzed 10 p-value thresholds: 5 × 10−8, 1 × 10−7, 1 × 10−6, 1 × 10−5, 1 × 10−4, 0.001, 0.05, 0.3, 0.5, and 1, and clumped the AUD summary data by LD with r2 < 0.3 in a 500-kb window. Then we tested the association between AUD PRS and AUDIT-P, corrected for age, sex, and 10 PCs. The analysis was performed using PRSice-2 [51].