PT  - JOURNAL ARTICLE
AU  - Simone de Jong
AU  - Mateus Jose Abdalla Diniz
AU  - Andiara Calado Saloma Rodrigues
AU  - Ary Gadelha
AU  - Marcos L Santoro
AU  - Vanessa K Ota
AU  - Cristiano Noto
AU  - Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium
AU  - Charles Curtis
AU  - Hamel Patel
AU  - Lynsey S Hall
AU  - Paul F O`Reilly
AU  - Sintia I Belangero
AU  - Rodrigo Bressan
AU  - Gerome Breen
TI  - Applying polygenic risk scoring for psychiatric disorders within a family context
AID  - 10.1101/103713
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 103713
4099  - http://biorxiv.org/content/early/2017/02/06/103713.short
4100  - http://biorxiv.org/content/early/2017/02/06/103713.full
AB  - We aim to investigate the application of polygenic risks scoring within a family context and thereby unravel 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~300) in which 30% of family members have major depressive disorder or bipolar disorder. The polygenic risk scores illuminate patterns of assortative mating and anticipation, whereby increased polygenic risk for psychiatric disorders is contributed by affected individuals who married into the family, thereby increasing genetic risk over generations in the family. This may explain the observation of anticipation in mood disorder, 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.