to disorder-specific genetic factors. With this in mind, we applied and compared two strategies for combining information across clinical phenotypes. The first is a simple CC approach, comparing cases defined as having “any AD” against supernormal controls. The second applied multivariate modeling of the covariation among the ADs using the common factor model to define a single continuous dimension of liability for which quantitative scores can be estimated for each subject. Our group has applied this approach in prior candidate gene association studies (18) and in a pilot GWAS in the MGS sample (38), but this is the first such application in a large GWAS meta-analysis. We note that this strategy is consistent with NIMH’s Research Domain Criteria (RDoC) initiative, which aims to serve as a framework for new approaches to research on mental disorders based on fundamental dimensions that cut across traditional disorder categories and more closely align with mechanisms that underlie psychopathology at various biological levels from genes to neural circuits (39). Also important to note is that ADs not only share genetic risk factors amongst themselves but also with other internalizing phenotypes like MDD (15), obsessive compulsive disorder (40), and personality traits like neuroticism and extroversion (41).
