title: Increased exonic de novo mutation rate in individuals with schizophrenia.
abstract: Schizophrenia is a severe psychiatric disorder that profoundly affects cognitive, behavioral and emotional processes. The wide spectrum of symptoms and clinical variability in schizophrenia suggest a complex genetic etiology, which is consistent with the numerous loci thus far identified by linkage, copy number variation and association studies. Although schizophrenia heritability may be as high as ∼80%, the genes responsible for much of this heritability remain to be identified. Here we sequenced the exomes of 14 schizophrenia probands and their parents. We identified 15 de novo mutations (DNMs) in eight probands, which is significantly more than expected considering the previously reported DNM rate. In addition, 4 of the 15 identified DNMs are nonsense mutations, which is more than what is expected by chance. Our study supports the notion that DNMs may account for some of the heritability reported for schizophrenia while providing a list of genes possibly involved in disease pathogenesis.
authors: Centre of Excellence in Neuromics of Université de Montréal, Centre Hospitalier de l'Université de Montréal Research Center, Montréal, Québec, Canada.
authors: Simon L
authors: SL
authors: Girard
authors: Julie
authors: J
authors: Gauthier
authors: Anne
authors: A
authors: Noreau
authors: Lan
authors: L
authors: Xiong
authors: Sirui
authors: S
authors: Zhou
authors: Loubna
authors: L
authors: Jouan
authors: Alexandre
authors: A
authors: Dionne-Laporte
authors: Dan
authors: D
authors: Spiegelman
authors: Edouard
authors: E
authors: Henrion
authors: Ousmane
authors: O
authors: Diallo
authors: Pascale
authors: P
authors: Thibodeau
authors: Isabelle
authors: I
authors: Bachand
authors: Jessie Y J
authors: JY
authors: Bao
authors: Amy Hin Yan
authors: AH
authors: Tong
authors: Chi-Ho
authors: CH
authors: Lin
authors: Bruno
authors: B
authors: Millet
authors: Nematollah
authors: N
authors: Jaafari
authors: Ridha
authors: R
authors: Joober
authors: Patrick A
authors: PA
authors: Dion
authors: Si
authors: S
authors: Lok
authors: Marie-Odile
authors: MO
authors: Krebs
authors: Guy A
authors: GA
authors: Rouleau
mesh_terms: D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D009154:Mutation; D010375:Pedigree; D012559:Schizophrenia / Q000235:genetics*