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Chunk #27 — Methods — Analysis Plan — Validation Analysis: Polygenic Scores

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A Developmentally-Informative Genome-wide Association Study of Alcohol Use Frequency.
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PGS were constructed from the gSEM GWAS of the residuals and common factor using PRS-CS (Ge et al. 2019). The ϕ global shrinkage parameter was set to 1e-2 to accommodate the small sample size of the meta-analyzed GWAS in adolescence, early adulthood, and adulthood. All PGS were scaled to a standard normal distribution with a mean of 0 and a standard deviation of 1. A series of mixed effects models with random intercepts for family group were used to assess the effect of the age-specific PGS and the common factor PGS on the corresponding phenotype in COGA using the lme4 (Bates et al. 2015) and lmerTest packages (Kuznetsova et al. 2017) in R (R Core Team, 2017). A separate mixed effects model was used for each developmental period included in the gSEM GWAS. Sex, birth year, genotyping array, and 10 PCs were included as covariates in each model. Individual proband status was included as a covariate in early adulthood and adulthood. The Benjamini-Hochberg procedure for controlling the False Discovery Rate (FDR) (Benjamini & Hochberg, 1995) was implemented to correct p-values