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However, the role of common polygenic risk in multiplex families has not previously been examined. The present study examined 249 European\u2010ancestry families from the NIMH Genetics Initiative sample, comparing subjects with narrowly defined BP (excluding bipolar II and recurrent unipolar depression; n\u2009=\u2009601) and their adult relatives without BP (n\u2009=\u2009695). Unrelated adult controls (n\u2009=\u2009266) were from the NIMH TGEN control dataset. We also examined a prospective cohort of young (12\u201330 years) offspring and siblings of individuals with BPI and BPII disorder (at risk; n\u2009=\u2009367) and psychiatrically screened controls (n\u2009=\u2009229), ascertained from five sites in the US and Australia and assessed with standardized clinical protocols. Thirty\u2010two disease\u2010associated SNPs from the PGC\u2010BP Working Group report (2011) were genotyped and additive polygenic risk scores (PRS) derived. We show increased PRS in adult cases compared to unrelated controls (<jats:italic>P<\/jats:italic>\u2009=\u20093.4\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>, AUC\u2009=\u20090.60). In families with a high\u2010polygenic load (PRS score \u226532 in two or more subjects), PRS distinguished cases with BPI\/SAB from other relatives (<jats:italic>P<\/jats:italic>\u2009=\u20090.014, RR\u2009=\u20091.32). Secondly, a higher PRS was observed in at\u2010risk youth, regardless of affected status, compared to unrelated controls (GEE\u2010\u03c7<jats:sup>2<\/jats:sup>\u2009=\u20095.15, <jats:italic>P<\/jats:italic>\u2009=\u20090.012). This report is the first to explore common polygenic risk in multiplex families, albeit using only a small number of robustly associated risk variants. We show that individuals with BP have a higher load of common disease\u2010associated variants than unrelated controls and first\u2010degree relatives, and illustrate the potential utility of PRS assessment in a family context. \u00a9 2015 The Authors. <jats:italic>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics<\/jats:italic> Published by Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32344","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T05:18:59Z","timestamp":1437023939000},"page":"617-629","source":"Crossref","is-referenced-by-count":47,"title":["Assessment of first and second degree relatives of individuals with bipolar disorder shows increased genetic risk scores in both affected relatives and young At\u2010Risk Individuals"],"prefix":"10.1002","volume":"168","author":[{"given":"Janice M.","family":"Fullerton","sequence":"first","affiliation":[{"name":"Neuroscience Research Australia Randwick Sydney New South Wales Australia"},{"name":"School of Medical Sciences University of New South Wales Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Koller","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University Indiana Indianapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard J.","family":"Edenberg","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University Indiana Indianapolis"},{"name":"Department of Biochemistry and Molecular Biology and Center for Medical Genomics Indiana University Indiana Indianapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Foroud","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University Indiana Indianapolis"},{"name":"Department of Psychiatry, Institute of Psychiatric Research Indiana University School of Medicine Indiana Indianapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Indiana University School of Medicine Indiana Indianapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne L.","family":"Glowinski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melvin G.","family":"McInnis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly C.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Child Psychiatry &amp; Public Health Johns Hopkins University Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Frankland","sequence":"additional","affiliation":[{"name":"School of Psychiatry University of New South Wales Sydney New South Wales Australia"},{"name":"Black Dog Institute Prince of Wales Hospital Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Roberts","sequence":"additional","affiliation":[{"name":"School of Psychiatry University of New South Wales Sydney New South Wales Australia"},{"name":"Black Dog Institute Prince of Wales Hospital Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Schofield","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia Randwick Sydney New South Wales Australia"},{"name":"School of Medical Sciences University of New South Wales Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip B.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"School of Psychiatry University of New South Wales Sydney New South Wales Australia"},{"name":"Black Dog Institute Prince of Wales Hospital Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John I.","family":"Nurnberger","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University Indiana Indianapolis"},{"name":"Department of Psychiatry, Institute of Psychiatric Research Indiana University School of Medicine Indiana Indianapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Bipolar High Risk Study Group, BiGS Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11632"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.37"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4002012"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2008.16"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.03.033"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2012.02.016"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2579"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2011.157"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.01.017"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60855-7"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/376562"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003348"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp295"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.209"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.10.022"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-200104000-00014"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2013.12081129"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.110.087866"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199707000-00021"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1982.04290080001001"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1108"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2711"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.02.002"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60072-6"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2088"},{"key":"e_1_2_9_27_1","unstructured":"MaxwellME.1992. 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