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Chunk #10 — METHODS — Polygenic score analyses

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Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.
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We created polygenic scores for DSM-NicDep and FTND in the European ancestry subset of the NESARC-III sample. NESARC-III was genotyped using the Affymetrix Axiom® Exome Array29, which limited our ability to impute SNPs due to lack of appreciable non-exonic coverage and resulted in some regions with low SNP densities. Details of QC and imputation are available in the Supplemental Materials. We used PRS-CS30, a Bayesian method that uses continuous shrinkage priors to weight SNP effect sizes, and used the ‘auto’ function, which allows the global scaling parameter to be automatically learned from the data. We then used the ‘score’ function in Plink 1.931 to create polygenic scores for DSM-NicDep and FTND in NESARC-III. The associations between DSM-5 tobacco use disorder, endorsement of the 11 individual diagnostic criteria, and 4 of the 6 FTND criteria (excluding cigarettes per day and smoking when ill) in NESARC-III (N = 12,482; Ncases = 4,205) and the polygenic scores for DSM-NicDep and FTND were estimated using logistic regression models in R, covarying for age, sex, and 10 within-ancestry principal components. Both polygenic scores were included jointly as predictors in the same model.