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Chunk #16 — Materials and Methods — Data Analysis — Discovery GWAS

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Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across Population-Based and Clinically Ascertained Samples.
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In ALSPAC and IASPSAD, GWAS of the alcohol problems phenotypes described above have previously been reported (Edwards et al., 2015; Adkins et al., 2017). Covariates included in these analyses were sex (both studies) and age (IASPSAD; ALSPAC was age-standardized). We use SNP-level summary statistics from those reports to create polygenic risk scores. In FT12 and COGA, we conducted a GWAS of DSM-IV alcohol dependence symptom counts, using residuals of these symptom counts after the effects of relevant covariates were regressed out. These covariates included sex for the age-standardized FT12 sample, and sex, age at maximum AUD symptoms, and the first two ancestry principal components for COGA. These analyses were run in the GenABEL package (Aulchenko et al., 2007) for R version 3.2.1 (R Core Team, 2015), using the polygenic (Thompson and Shaw, 1990) and mmscore (Chen and Abecasis, 2007) procedures to control for the non-independence of related subjects, in parallel to the methods used in the IASPSAD GWAS. In FT12, one twin from MZ pairs was excluded from the GWAS for a total discovery n = 905. In both FT12