LAUSR

Abstract As part of a five-site collaborative study, we are following 300 adolescents/young adults at high risk for bipolar disorder and related conditions (because they are close relatives of a bipolar proband), along with 150 age-matched controls. A new follow-up protocol is beginning over the next several months. The risk for major mood disorder is ~35% for high risk offspring and ~7% for controls. An additional reference sample, available for studies of course of illness is the BiGS sample, including > 600 families with multiple cases of bipolar disorder and >4000 unrelated bipolar cases. Using these three samples (high risk, familial BP, case BP) we describe the development of a clinical subtyping scheme and its potential use in predicting risk and course of illness. We have now obtained complete, newly imputed, genotype data from the PGC on all of our cases and ethnically matched controls, as well as the high risk sample. These data are being used to develop polygenic risk scores for use in prediction of illness (as part of the research, not for clinical purposes currently). We are also using the genotype data in conjunction with our published work on bipolar pathways (Nurnberger et al, JAMA Psychiatry, 2014) in order to derive pathway-specific polygenic risk scores. These will be applied to BPI cases in general and to the specific subtypes we have described (Monahan et al, Psychological Medicine, 2015): 1) pure BPI, 2) BPI plus internalizing disorder, 3) BPI plus externalizing disorder, and 4) BPI plus externalizing and internalizing disorder.