title: Association of genetic variants of GRIN2B with autism.
abstract: Autism (MIM 209850) is a complex neurodevelopmental disorder characterized by social communication impairments and restricted repetitive behaviors. It has a high heritability, although much remains unclear. To evaluate genetic variants of GRIN2B in autism etiology, we performed a system association study of common and rare variants of GRIN2B and autism in cohorts from a Chinese population, involving a total sample of 1,945 subjects. Meta-analysis of a triad family cohort and a case-control cohort identified significant associations of multiple common variants and autism risk (Pmin = 1.73 × 10(-4)). Significantly, the haplotype involved with the top common variants also showed significant association (P = 1.78 × 10(-6)). Sanger sequencing of 275 probands from a triad cohort identified several variants in coding regions, including four common variants and seven rare variants. Two of the common coding variants were located in the autism-related linkage disequilibrium (LD) block, and both were significantly associated with autism (P < 9 × 10(-3)) using an independent control cohort. Burden analysis and case-only analysis of rare coding variants identified by Sanger sequencing did not find this association. Our study for the first time reveals that common variants and related haplotypes of GRIN2B are associated with autism risk.
authors: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors: Yongcheng
authors: Y
authors: Pan
authors: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors: Jingjing
authors: J
authors: Chen
authors: 1] The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China [2] Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors: Hui
authors: H
authors: Guo
authors: Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors: Jianjun
authors: J
authors: Ou
authors: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors: Yu
authors: Y
authors: Peng
authors: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors: Qiong
authors: Q
authors: Liu
authors: Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors: Yidong
authors: Y
authors: Shen
authors: Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors: Lijuan
authors: L
authors: Shi
authors: 1] The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China [2] The Xiangya Hospital, Central South University, Hunan, China.
authors: Yalan
authors: Y
authors: Liu
authors: 1] The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China [2] The Third Xiangya Hospital, Central South University, Hunan, China.
authors: Zhimin
authors: Z
authors: Xiong
authors: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors: Tengfei
authors: T
authors: Zhu
authors: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors: Sanchuan
authors: S
authors: Luo
authors: The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
authors: Zhengmao
authors: Z
authors: Hu
authors: Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors: Jingping
authors: J
authors: Zhao
authors: 1] The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China [2] College of Life Science and Technology, Xinjiang University, Xinjiang, China [3] Key Laboratory of Medical Information Research (Central South University), Changsha, Hunan, China.
authors: Kun
authors: K
authors: Xia
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001321:Autistic Disorder / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate
references: Nature. 2012 Apr 04;485(7397):246-50
references: 22495309
references: Nat Genet. 2014 Aug;46(8):881-5
references: 25038753
references: Pharmacol Rev. 1999 Mar;51(1):7-61
references: 10049997
references: MMWR Surveill Summ. 2012 Mar 30;61(3):1-19
references: 22456193
references: Curr Opin Neurobiol. 2009 Apr;19(2):231-4
references: 19545994
references: Transl Psychiatry. 2011 Nov 15;1:e55
references: 22833210
references: Mol Psychiatry. 2014 Nov;19(11):1212-9
references: 24189344
references: Lancet. 2009 Nov 7;374(9701):1627-38
references: 19819542
references: Bioinformatics. 2005 Jan 15;21(2):263-5
references: 15297300
references: Mol Neurobiol. 2011 Aug;44(1):71-82
references: 21604197
references: Trends Genet. 2010 Aug;26(8):363-72
references: 20609491
references: Nature. 2006 Mar 23;440(7083):456-62
references: 16554805
references: Nat Genet. 2011 Jun;43(6):585-9
references: 21572417
references: Science. 2012 Sep 7;337(6099):1190-5
references: 22955828
references: Am J Hum Genet. 2007 Sep;81(3):559-75
references: 17701901
references: Curr Probl Pediatr Adolesc Health Care. 2013 Jan;43(1):2-11
references: 23332397
references: Cell. 1998 Jan 23;92(2):279-89
references: 9458051