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: https://orcid.org/0000-0003-4083-1143, 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: https://orcid.org/0000-0002-5122-8334, 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

Preview

Text Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview

Abstract

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.

Actions (login required)

View Item