Common genetic variants on 1p13.2 associate with risk of autism

K Xia; H Guo; Z Hu; G Xun; L Zuo; Y Peng; K Wang; Y He; Z Xiong; L Sun; Q Pan; Z Long; X Zou; X Li; W Li; X Xu; L Lu; Y Liu; Y Hu; D Tian; L Long; J Ou; Y Liu; X Li; L Zhang; Y Pan; J Chen; H Peng; Q Liu; X Luo; W Su; L Wu; D Liang; H Dai; X Yan; Y Feng; B Tang; J Li; Z Miedzybrodzka; J Xia; Z Zhang; X Luo; X Zhang; D St Clair; J Zhao; F Zhang

doi:10.1038/mp.2013.146

Common genetic variants on 1p13.2 associate with risk of autism

Mol Psychiatry. 2014 Nov;19(11):1212-9. doi: 10.1038/mp.2013.146. Epub 2013 Nov 5.

Authors

K Xia¹, H Guo², Z Hu¹, G Xun³, L Zuo⁴, Y Peng¹, K Wang⁵, Y He³, Z Xiong¹, L Sun⁵, Q Pan⁶, Z Long⁶, X Zou⁷, X Li⁶, W Li⁶, X Xu⁶, L Lu⁶, Y Liu⁶, Y Hu⁶, D Tian⁶, L Long⁶, J Ou³, Y Liu³, X Li³, L Zhang⁶, Y Pan⁶, J Chen⁶, H Peng⁶, Q Liu⁶, X Luo³, W Su⁶, L Wu⁶, D Liang⁶, H Dai⁶, X Yan⁸, Y Feng⁸, B Tang⁸, J Li¹, Z Miedzybrodzka⁹, J Xia⁶, Z Zhang⁶, X Luo⁴, X Zhang⁵, D St Clair¹⁰, J Zhao¹¹, F Zhang¹²

Affiliations

¹ 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.
² 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.
³ Mental Health Institute, The Second Xiangya Hospital, Central South University, Hunan, China.
⁴ Department of Psychiatry, Yale University, New Haven, CT, USA.
⁵ State Key Laboratory Incubation Base of Dermatology, Anhui, China.
⁶ State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
⁷ Department of Pediatrics, No. 3 Hospital of the Sun Yat-sen University, Guangdong, China.
⁸ 1] State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China [2] The Xiangya Hospital, Central South University, Hunan, China.
⁹ University of Aberdeen, Royal Cornhill Hospital, Aberdeen, UK.
¹⁰ 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.
¹¹ 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.
¹² 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.

PMID: 24189344
DOI: 10.1038/mp.2013.146

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.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Asian People / genetics
Autistic Disorder / genetics*
Autistic Disorder / metabolism
Black or African American
China
Chromosomes, Human, Pair 1 / genetics*
Cohort Studies
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
GTP Phosphohydrolases / genetics*
GTP Phosphohydrolases / metabolism
Genetic Predisposition to Disease*
Genome-Wide Association Study
Haplotypes
Humans
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Meta-Analysis as Topic
Polymorphism, Single Nucleotide*
Prefrontal Cortex / metabolism
RNA-Binding Proteins / genetics*
RNA-Binding Proteins / metabolism
Risk
Transcription Factors / genetics*
Transcription Factors / metabolism
White People / genetics

Substances

CSDE1 protein, human
DNA-Binding Proteins
Membrane Proteins
RNA-Binding Proteins
TRIM33 protein, human
Transcription Factors
GTP Phosphohydrolases
NRAS protein, human

Grants and funding

Intramural NIH HHS/United States