University of Worcester Worcester Research and Publications

Evidence For Genetic Heterogeneity Between Clinical Subtypes of Bipolar Disorder

Charney, A.W., Ruderfer, D.M., Stahl, E.A., Moran, J.L., Chambert, K., Belliveau, R., Forty, L., Gordon-Smith, Katherine ORCID:, Di Florio, A., Lee, P.H., Bromet, E.J., Buckley, P.F., Escamilla, M.A., Fanous, A.H., Fochtmann, L.J., Lehrer, D.S., Malaspina, D., Marder, S.R., Morley, C.P., Nicolini, H., Perkins, D.O., Rakofsky, J.J., Rapaport, M.H., Medeiros, H., Sobell, J.L., Green, E.K., Backlund, L., Bergen, S.E., Juréus, A., Schalling, M., Lichtenstein, P., Roussos, P., Knowles, J.A., Jones, Lisa ORCID:, Hultman, C.M., Perlis, R., Purcell, S.M., McCarroll, S.A., Pato, C.N., Pato, M.T., Craddock, N., Landén, M., Smoller, J.W. and Sklar, P. (2017) Evidence For Genetic Heterogeneity Between Clinical Subtypes of Bipolar Disorder. Translational Psychiatry, 7 (e993). ISSN 2158-3188

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We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide
significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P = 3.28 × 10 − 8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P
(XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia (SCZ) and major depressive disorder. We found a significant difference in heritability of the two
most common forms of BD (BD I h2 = 0.35; BD II h2 = 0.25; P = 0.02) with a genetic correlation between BD I and BD II of 0.78,compared with a genetic correlation of 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for SCZ and BD in patients with BD I compared with patients with BD II, and a
greater load of SCZ risk alleles in the bipolar type of schizoaffective disorder (SAB) compared with both other BD subtypes. These results point to a partial difference in genetic architecture of BD subtypes, and are suggestive of a molecular correlate for the
clinical division of BD into subtypes.

Item Type: Article
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Uncontrolled Discrete Keywords: Bipolar disorder, Genome-wide association (GWAS), clinical subtypes
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: College of Health, Life and Environmental Sciences > School of Allied Health and Community
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Copyright Info: Open Access article
Depositing User: Katherine Gordon-Smith
Date Deposited: 03 Jan 2017 10:01
Last Modified: 17 Jun 2020 17:15

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