title: Common genetic variants on 1p13.2 associate with risk of autism.
abstract: Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n=2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P=4.49 × 10(-8)), non-synonymous rs6537835 (P=3.26 × 10(-8)) and rs1877455 (P=8.70 × 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism.
authors.affiliation: 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] School of Biological Science and Technology, Central South University, Hunan, China.
authors.forename: K
authors.initials: K
authors.lastname: Xia
authors.affiliation: 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] School of Biological Science and Technology, Central South University, Hunan, China [3] Division of Intramural Research Programs, National Institute of Mental Health, The National Institutes of Health, Bethesda, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Guo
authors.affiliation: 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] School of Biological Science and Technology, Central South University, Hunan, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors.forename: G
authors.initials: G
authors.lastname: Xun
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zuo
authors.affiliation: 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] School of Biological Science and Technology, Central South University, Hunan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Anhui, China.
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.affiliation: Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.affiliation: 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] School of Biological Science and Technology, Central South University, Hunan, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Anhui, China.
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Long
authors.affiliation: Department of Pediatrics, No. 3 Hospital of the Sun Yat-sen University, Guangdong, China.
authors.forename: X
authors.initials: X
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: D
authors.initials: D
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: L
authors.initials: L
authors.lastname: Long
authors.affiliation: Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors.forename: J
authors.initials: J
authors.lastname: Ou
authors.affiliation: Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: H
authors.initials: H
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: W
authors.initials: W
authors.lastname: Su
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: D
authors.identifier: 0000000294518585
authors.initials: D
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: H
authors.initials: H
authors.lastname: Dai
authors.affiliation: 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] The Xiangya Hospital, Central South University, Hunan, China.
authors.forename: X
authors.initials: X
authors.lastname: Yan
authors.affiliation: 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] The Xiangya Hospital, Central South University, Hunan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.affiliation: 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] The Xiangya Hospital, Central South University, Hunan, China.
authors.forename: B
authors.initials: B
authors.lastname: Tang
authors.affiliation: 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] School of Biological Science and Technology, Central South University, Hunan, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: University of Aberdeen, Royal Cornhill Hospital, Aberdeen, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Miedzybrodzka
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: J
authors.initials: J
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Anhui, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1] Division of Intramural Research Programs, National Institute of Mental Health, The National Institutes of Health, Bethesda, MD, USA [2] University of Aberdeen, Royal Cornhill Hospital, Aberdeen, UK.
authors.forename: D
authors.initials: D
authors.lastname: St Clair
authors.affiliation: 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: 1] Division of Intramural Research Programs, National Institute of Mental Health, The National Institutes of Health, Bethesda, MD, USA [2] The Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
authors.forename: F
authors.initials: F
authors.lastname: Zhang
mesh_terms: D001741:Black or African American; D044466:Asian People / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics* / Q000378:metabolism; D002681:China; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: C079950:CSDE1 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C511956:TRIM33 protein, human; D014157:Transcription Factors; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human