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Chunk #68 — 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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We also tested the PRS of AUDIT-C and AUD for DSM-IV alcohol dependence criterion counts in the Yale-Penn cohort25. There are three phases of the Yale-Penn sample: phase 1 contains 3110 AAs and 1718 EAs exposed to alcohol; phase 2 contains 1667 AAs and 1689 EAs exposed to alcohol; phase 3 contains 556 AAs and 999 EAs exposed to alcohol. PRS were generated for EAs and AAs in each phase as described above and 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). Different from PRS in MVP and PMBB, to correct for the relatedness in the Yale-Penn subjects, a linear mixed model implemented in GEMMA66 was used to test the association between PRS score and DSM-IV alcohol dependence criterion counts, with age, sex, and the first 10 PCs as covariates. Meta-analyses of data from the three phases were performed in AAs (N = 5333) and EAs (N = 4406) separately.