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dc.contributor.authorFullerton, JM
dc.contributor.authorKoller, DL
dc.contributor.authorEdenberg, HJ
dc.contributor.authorForoud, T
dc.contributor.authorLiu, H
dc.contributor.authorGlowinski, AL
dc.contributor.authorMcInnis, MG
dc.contributor.authorWilcox, HC
dc.contributor.authorFrankland, A
dc.contributor.authorRoberts, G
dc.contributor.authorSchofield, PR
dc.contributor.authorMitchell, PB
dc.contributor.authorNurnberger, JI
dc.contributor.authorBipolar High Risk Study Group, BiGS Consortium
dc.date.accessioned2021-02-04T01:35:15Z
dc.date.available2021-02-04T01:35:15Z
dc.date.issued2015-10
dc.identifier.citationFullerton, J. M., Koller, D. L., Edenberg, H. J., Foroud, T., Liu, H., Glowinski, A. L., McInnis, M. G., Wilcox, H. C., Frankland, A., Roberts, G., Schofield, P. R., Mitchell, P. B., Nurnberger, J. I. & Bipolar High Risk Study Group, BiGS Consortium (2015). Assessment of first and second degree relatives of individuals with bipolar disorder shows increased genetic risk scores in both affected relatives and young At-Risk Individuals.. Am J Med Genet B Neuropsychiatr Genet, 168 (7), pp.617-629. https://doi.org/10.1002/ajmg.b.32344.
dc.identifier.issn1552-4841
dc.identifier.urihttp://hdl.handle.net/11343/259411
dc.description.abstractRecent studies have revealed the polygenic nature of bipolar disorder (BP), and identified common risk variants associated with illness. However, the role of common polygenic risk in multiplex families has not previously been examined. The present study examined 249 European-ancestry families from the NIMH Genetics Initiative sample, comparing subjects with narrowly defined BP (excluding bipolar II and recurrent unipolar depression; n = 601) and their adult relatives without BP (n = 695). Unrelated adult controls (n = 266) were from the NIMH TGEN control dataset. We also examined a prospective cohort of young (12-30 years) offspring and siblings of individuals with BPI and BPII disorder (at risk; n = 367) and psychiatrically screened controls (n = 229), ascertained from five sites in the US and Australia and assessed with standardized clinical protocols. Thirty-two disease-associated SNPs from the PGC-BP Working Group report (2011) were genotyped and additive polygenic risk scores (PRS) derived. We show increased PRS in adult cases compared to unrelated controls (P = 3.4 × 10(-5) , AUC = 0.60). In families with a high-polygenic load (PRS score ≥32 in two or more subjects), PRS distinguished cases with BPI/SAB from other relatives (P = 0.014, RR = 1.32). Secondly, a higher PRS was observed in at-risk youth, regardless of affected status, compared to unrelated controls (GEE-χ(2) = 5.15, P = 0.012). 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-associated variants than unrelated controls and first-degree relatives, and illustrate the potential utility of PRS assessment in a family context.
dc.languageeng
dc.publisherWiley
dc.titleAssessment of first and second degree relatives of individuals with bipolar disorder shows increased genetic risk scores in both affected relatives and young At-Risk Individuals.
dc.typeJournal Article
dc.identifier.doi10.1002/ajmg.b.32344
melbourne.affiliation.departmentCentre for Youth Mental Health
melbourne.affiliation.facultyCollected Works
melbourne.source.titleAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
melbourne.source.volume168
melbourne.source.issue7
melbourne.source.pages617-629
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1214334
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054905
melbourne.contributor.authorFISHER, CAROLINE
dc.identifier.eissn1552-485X
melbourne.accessrightsOpen Access


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