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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. ... view all 44 authors View less authors (2017)
Publisher: Macmillan Publishers Limited
Journal: Translational Psychiatry
Languages: English
Types: Article
Subjects: Original Article, RC0321, BF, R1
We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International\ud Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics\ud Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight\ud genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P = 3.28 × 10− 8)\ud that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific\ud aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and\ud investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability\ud of the two most common forms of BD (BD I SNP-h2 = 0.35; BD II SNP-h2 = 0.25; P = 0.02). The genetic correlation between BD I and\ud BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we\ud demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with\ud patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder\ud compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD\ud subtypes as currently defined.
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