RT Journal Article SR Electronic T1 Applying polygenic risk scoring for psychiatric disorders to a large family with Bipolar Disorder and Major Depressive Disorder JF bioRxiv FD Cold Spring Harbor Laboratory SP 103713 DO 10.1101/103713 A1 Simone de Jong A1 Mateus Jose Abdalla Diniz A1 Andiara Calado Saloma Rodrigues A1 Ary Gadelha A1 Marcos L Santoro A1 Vanessa K Ota A1 Cristiano Noto A1 Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium A1 Charles Curtis A1 Hamel Patel A1 Lynsey S Hall A1 Paul F O’Reilly A1 Sintia I Belangero A1 Rodrigo Bressan A1 Gerome Breen YR 2018 UL http://biorxiv.org/content/early/2018/02/06/103713.abstract AB We aim to investigate the application of polygenic risk scoring within a family context. Polygenic risk profiles could aid in unraveling the role that common variation confers on disease risk within a pedigree that would have traditionally been viewed through the prism of monogenic inheritance only. We illustrate our discussion by analyzing polygenic risk scores for schizophrenia, major depressive disorder and bipolar disorder in a large pedigree (n~260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. We apply polygenic risk scores to study patterns of assortative mating and anticipation, whereby it appears increased polygenic risk for psychiatric disorders is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations in the family. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity of a disease increases over the generations of a family. Joint analyses of both rare and common variation may be the most powerful way to understand the familial genetics of mood and psychiatric disorders.