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.A.; Forty, L.; Gordon-Smith, Katherine; 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; 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. (2016) Evidence For Genetic Heterogeneity Between Clinical Subtypes of Bipolar Disorder.

View this record at http://eprints.worc.ac.uk/5165/
Official URL: 10.1038/tp.2016.242


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
Keywords: BF Psychology, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Members: University of Worcester
Depositing User: ULCC Admin
Date Deposited: 04 Jan 2017 04:28
Last Modified: 16 Feb 2017 04:26
URI: http://collections.crest.ac.uk/id/eprint/14689

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