Two additional analytic considerations were made. First, there have been increasing concerns regarding the potential oversampling for susceptibility to smoking in a sub-component of the UK Biobank (the UK BiLEVE sample; see (Munafò et al., 2017)). To examine this possibility, alcohol consumption PRS were also regressed on a measure of maximum cigarettes smoked per day (however, any observed association might also reflect pleiotropy, given the genetic correlation between smoking and drinking). Second, even though pseudo-R2 is the most widely accepted index of predictive utility for PRS analyses of categorical outcomes, metrics such as Area Under the Curve (AUC) may provide a more conservative and precise estimate of their predictive capabilities for binary traits (Wray et al., 2013). Thus, we supplemented a subset of our analyses with estimates of AUC. Youden’s J index (sensitivity + specificity – 1) was used to generate the optimal cut-point in PRS for prediction of any significantly associated dichotomous traits (Youden, 1950).
