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

被引：79

作者：

Xia, K. ^{[1
,2
]}

Guo, H. ^{[1
,2
,3
]}

Hu, Z. ^{[1
,2
]}

Xun, G. ^{[4
]}

Zuo, L. ^{[5
]}

Peng, Y. ^{[1
,2
]}

Wang, K. ^{[6
]}

He, Y. ^{[4
]}

Xiong, Z. ^{[1
,2
]}

Sun, L.

Pan, Q. ^{[1
]}

Long, Z. ^{[1
]}

Zou, X. ^{[7
]}

Li, X. ^{[1
,4
]}

Li, W. ^{[1
]}

Xu, X. ^{[1
]}

Lu, L. ^{[1
]}

Liu, Y. ^{[1
,4
]}

Hu, Y. ^{[1
]}

Tian, D. ^{[1
]}

Long, L. ^{[1
]}

Ou, J. ^{[4
]}

Liu, Y. ^{[1
,4
]}

Li, X. ^{[1
,4
]}

Zhang, L. ^{[1
]}

Pan, Y. ^{[1
]}

Chen, J. ^{[1
]}

Peng, H. ^{[1
]}

Liu, Q. ^{[1
]}

Luo, X. ^{[4
,5
]}

Su, W. ^{[1
]}

Wu, L. ^{[1
]}

Liang, D. ^{[1
]}

Dai, H. ^{[1
]}

Yan, X. ^{[1
,8
]}

Feng, Y. ^{[1
,8
]}

Tang, B. ^{[1
,8
]}

Li, J. ^{[1
]}

Miedzybrodzka, Z. ^{[9
]}

Xia, J. ^{[1
]}

Zhang, Z. ^{[1
]}

Luo, X. ^{[4
,5
]}

Zhang, X. ^{[6
]}

St Clair, D. ^{[3
,9
]}

Zhao, J. ^{[1
,4
]}

Zhang, F. ^{[3
,10
]}

机构：

[1] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China

[2] Cent S Univ, Sch Biol Sci & Technol, Changsha 410078, Hunan, Peoples R China

[3] NIMH, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA

[4] Cent S Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha 410078, Hunan, Peoples R China

[5] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA

[6] State Key Lab Incubation Base Dermatol, Hefei, Anhui, Peoples R China

[7] Sun Yat Sen Univ, Hosp 3, Dept Pediat, Guangzhou, Guangdong, Peoples R China

[8] Cent S Univ, Xiangya Hosp, Changsha 410078, Hunan, Peoples R China

[9] Univ Aberdeen, Royal Cornhill Hosp, Aberdeen, Scotland

[10] Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD USA

来源：

MOLECULAR PSYCHIATRY | 2014年 / 19卷 / 11期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

association fine mapping; autism; common genetic variants; genome-wide association study; human genetics; COPY NUMBER VARIATION; GENOME-WIDE LINKAGE; DE-NOVO MUTATIONS; SPECTRUM; UBIQUITIN; REVEALS; SCAN; ENCODES; COMPLEX; CUL4B;

D O I：

10.1038/mp.2013.146

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 x 10(-8) ), non-synonymous rs6537835 (P = 3.26 x 10(-8)) and rs1877455 (P = 8.70 x 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.

引用

页码：1212 / 1219

页数：8

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