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

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

Author information

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.

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.

PMID:
24189344
DOI:
10.1038/mp.2013.146
[Indexed for MEDLINE]

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