title: Association analysis of a functional variant in ATXN2 with schizophrenia.
abstract: Schizophrenia (SZ) is a severe mental disorder characterized by multiple neurodevelopmental dysfunctions including a breakdown of thinking process and a deficit of typical emotional responses. Ataxin-2 (ATXN2) plays vital roles in cell proliferation and growth, and functional mutations of ATXN2 cause neurodegenerative phenotypes, including spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS). To explore the possible role of ATXN2 in SZ, we conducted a two-stage study to examine the association of ATXN2 polymorphisms with SZ in the Han Chinese population. Association analysis of seven SNPs in 768 patients and 1348 controls revealed two associated SNPs, including rs630511 (P=1.76E-4) and rs7969300 (P=5.08E-4). We examined these two SNPs in a validation sample of 1957 patients and 1509 controls, and observed an association of rs7969300 with SZ (P=5.03E-3). The SNP rs7969300 is a non-synonymous SNP causing a Ser to Asn substitution, which is predicted to increase the protein stability of ATXN2. Our data suggest that the ATXN2 gene may confer vulnerability for SZ, adding further evidence for the genetic variants within the developmental pathway in the illness.
authors: Wuxi Mental Health Center, Wuxi, Jiangsu Province, China; Institute of Mental Health, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Beijing, China.
authors: Fuquan
authors: F
authors: Zhang
authors: Wuxi Mental Health Center, Wuxi, Jiangsu Province, China.
authors: Guoqiang
authors: G
authors: Wang
authors: Unit on Statistical Genomics, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States.
authors: Yin Yao
authors: YY
authors: Shugart
authors: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
authors: Yong
authors: Y
authors: Xu
authors: Institute of Mental Health, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Beijing, China.
authors: Chenxing
authors: C
authors: Liu
authors: Institute of Mental Health, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Beijing, China.
authors: Lifang
authors: L
authors: Wang
authors: Institute of Mental Health, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Beijing, China.
authors: Tianlan
authors: T
authors: Lu
authors: Institute of Mental Health, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Beijing, China.
authors: Hao
authors: H
authors: Yan
authors: Institute of Mental Health, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Beijing, China.
authors: Yanyan
authors: Y
authors: Ruan
authors: Wuxi Mental Health Center, Wuxi, Jiangsu Province, China.
authors: Zaohuo
authors: Z
authors: Cheng
authors: Wuxi Mental Health Center, Wuxi, Jiangsu Province, China.
authors: Lin
authors: L
authors: Tian
authors: Wuxi Mental Health Center, Wuxi, Jiangsu Province, China.
authors: Chunhui
authors: C
authors: Jin
authors: Wuxi Mental Health Center, Wuxi, Jiangsu Province, China.
authors: Janmin
authors: J
authors: Yuan
authors: Wuxi Mental Health Center, Wuxi, Jiangsu Province, China.
authors: Zhiqiang
authors: Z
authors: Wang
authors: Wuxi Mental Health Center, Wuxi, Jiangsu Province, China.
authors: Wei
authors: W
authors: Zhu
authors: Wuxi Mental Health Center, Wuxi, Jiangsu Province, China.
authors: Leiming
authors: L
authors: Cao
authors: Wuxi Mental Health Center, Wuxi, Jiangsu Province, China.
authors: Yansong
authors: Y
authors: Liu
authors: Institute of Mental Health, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Beijing, China. Electronic address: dyue@bjmu.edu.cn.
authors: Weihua
authors: W
authors: Yue
authors: Institute of Mental Health, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Beijing, China. Electronic address: daizhang@bjmu.edu.cn.
authors: Dai
authors: D
authors: Zhang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D044466:Asian People / Q000235:genetics; D000067528:Ataxins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins
keywords: ATXN2; Schizophrenia; rs7969300