Rare structural variation of synapse and neurotransmission genes in autism

被引：113

作者：

Gai, X. ^{[1
]}

Xie, H. M. ^{[1
]}

Perin, J. C. ^{[1
]}

Takahashi, N. ^{[2
,3
]}

Murphy, K. ^{[1
]}

Wenocur, A. S. ^{[1
]}

D'arcy, M. ^{[1
]}

O'Hara, R. J. ^{[1
]}

Goldmuntz, E. ^{[4
,7
]}

Grice, D. E. ^{[5
]}

Shaikh, T. H. ^{[6
]}

Hakonarson, H. ^{[7
,8
,9
]}

Buxbaum, J. D. ^{[2
,3
]}

Elia, J. ^{[10
,11
]}

White, P. S. ^{[1
,7
,12
]}

机构：

[1] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA

[2] Mt Sinai Sch Med, Seaver Autism Ctr, New York, NY USA

[3] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA

[4] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA

[5] Columbia Univ, Dept Child & Adolescent Psychiat, New York, NY USA

[6] Univ Colorado, Sch Med, Dept Pediat, Denver, CO USA

[7] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

[8] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

[9] Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA

[10] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat, Philadelphia, PA 19104 USA

[11] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA

[12] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA

来源：

MOLECULAR PSYCHIATRY | 2012年 / 17卷 / 04期

关键词：

autism; copy-number variation; glutamatergic signaling; neurotransmission; structural variation; synaptic transmission; COPY-NUMBER VARIATION; ALPHA-NEUREXINS; ASSOCIATION; GENOME; LINKAGE; POLYMORPHISM; GENETICS; SPECTRUM; CHANNEL; DOMAIN;

D O I：

10.1038/mp.2011.10

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 spectrum disorders (ASDs) comprise a constellation of highly heritable neuropsychiatric disorders. Genome-wide studies of autistic individuals have implicated numerous minor risk alleles but few common variants, suggesting a complex genetic model with many contributing loci. To assess commonality of biological function among rare risk alleles, we compared functional knowledge of genes overlapping inherited structural variants in idiopathic ASD subjects relative to healthy controls. In this study we show that biological processes associated with synapse function and neurotransmission are significantly enriched, with replication, in ASD subjects versus controls. Analysis of phenotypes observed for mouse models of copy-variant genes established significant and replicated enrichment of observable phenotypes consistent with ASD behaviors. Most functional terms retained significance after excluding previously reported ASD loci. These results implicate several new variants that involve synaptic function and glutamatergic signaling processes as important contributors of ASD pathophysiology and suggest a sizable pool of additional potential ASD risk loci. Molecular Psychiatry (2012) 17, 402-411; doi: 10.1038/mp.2011.10; published online 1 March 2011

引用

页码：402 / 411

页数：10

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