To conduct PheWAS, we extracted ICD-9 data from the EHR for 353,323 genotyped veterans. Of these, 277,531 individuals had two or more separate encounters in the VA Healthcare System in each of the 2 years prior to enrollment in MVP, consisting of 21,209,658 records. ICD-9 codes were aggregated to phecodes using the PheWAS R package to create 1812 phecodes. To improve the specificity of these codes, individuals with at least two instances of the phecode were considered cases, those with no instance of the phecode controls, and those with one instance of a phecode or a related phecode as other. A PheWAS using logistic regression models with either AUDIT-C or AUD PRS as the independent variable, phecodes as the dependent variables, and age, sex and the first five PCs as covariates were used to identify secondary phenotypic associations. A phenome-wide significance threshold of 2.96 × 10−5 was applied to account for multiple testing.
