Contribution of Rare Copy Number Variants to Bipolar Disorder Risk Is Limited to Schizoaffective Cases.
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Charney Alexander W, Stahl Eli A, Green Elaine K, Chen Chia-Yen, Moran Jennifer L, Chambert Kimberly, Belliveau Richard A, Forty Liz, Gordon-Smith Katherine, Lee Phil H, Bromet Evelyn J, Buckley Peter F, Escamilla Michael A, Fanous Ayman H, Fochtmann Laura J, Lehrer Douglas S, Malaspina Dolores, Marder Stephen R, Morley Christopher P, Nicolini Humberto, Perkins Diana O, Rakofsky Jeffrey J, Rapaport Mark H, Medeiros Helena, Sobell Janet L, Backlund Lena, Bergen Sarah E, Juréus Anders, Schalling Martin, Lichtenstein Paul, Knowles James A, Burdick Katherine E, Jones Ian, Jones Lisa A, Hultman Christina M, Perlis Roy, Purcell Shaun M, McCarroll Steven A, Pato Carlos N, Pato Michele T, Di Florio Ariana, Craddock Nick, Landén Mikael, Smoller Jordan W, Ruderfer Douglas M, Sklar Pamela
Аннотация
METHODS: Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.
RESULTS: CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 × 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden.
CONCLUSIONS: CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.