Common genetic variants on 5p14.1 associate with autism spectrum disorders

被引：698

作者：

Wang, Kai ^{[1
]}

Zhang, Haitao ^{[1
]}

Ma, Deqiong ^{[2
,3
]}

Bucan, Maja ^{[4
]}

Glessner, Joseph T. ^{[1
]}

Abrahams, Brett S. ^{[5
,6
]}

Salyakina, Daria ^{[2
,3
]}

Imielinski, Marcin ^{[1
]}

Bradfield, Jonathan P. ^{[1
]}

Sleiman, Patrick M. A. ^{[1
]}

Kim, Cecilia E. ^{[1
]}

Hou, Cuiping ^{[1
]}

Frackelton, Edward ^{[1
]}

Chiavacci, Rosetta ^{[1
]}

Takahashi, Nagahide ^{[7
]}

Sakurai, Takeshi ^{[7
]}

Rappaport, Eric ^{[8
]}

Lajonchere, Clara M. ^{[9
]}

Munson, Jeffrey ^{[10
]}

Estes, Annette ^{[10
]}

Korvatska, Olena ^{[10
]}

Piven, Joseph ^{[11
,12
]}

Sonnenblick, Lisa I. ^{[5
,6
]}

Retuerto, Ana I. Alvarez ^{[5
,6
]}

Herman, Edward I. ^{[5
,6
]}

Dong, Hongmei ^{[5
,6
]}

Hutman, Ted ^{[5
,6
]}

Sigman, Marian ^{[5
,6
]}

Ozonoff, Sally ^{[13
,14
]}

Klin, Ami ^{[15
,16
]}

Owley, Thomas ^{[17
,18
]}

Sweeney, John A. ^{[17
,18
]}

Brune, Camille W. ^{[17
,18
]}

Cantor, Rita M. ^{[19
]}

Bernier, Raphael ^{[10
]}

Gilbert, John R. ^{[2
,3
]}

Cuccaro, Michael L. ^{[2
,3
]}

McMahon, William M. ^{[20
]}

Miller, Judith ^{[20
]}

State, Matthew W. ^{[15
,16
]}

Wassink, Thomas H. ^{[21
]}

Coon, Hilary ^{[20
]}

Levy, Susan E. ^{[8
]}

Schultz, Robert T. ^{[8
]}

Nurnberger, John I., Jr. ^{[22
]}

Haines, Jonathan L. ^{[23
]}

Sutcliffe, James S. ^{[24
,25
]}

Cook, Edwin H. ^{[17
,18
]}

Minshew, Nancy J. ^{[26
,27
]}

Buxbaum, Joseph D. ^{[7
,28
,29
,30
]}

机构：

[1] Childrens Hosp Philadelphia, Ctr Appl Gen, Philadelphia, PA 19104 USA

[2] Univ Miami, Miami Inst Human Genom, Miami, FL 33101 USA

[3] Univ Miami, Dept Human Genet, Miami, FL 33101 USA

[4] Univ Penn, Dept Genet, Philadelphia, PA 19014 USA

[5] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Ctr Autism Res & Treatment, Los Angeles, CA 90095 USA

[7] Mt Sinai Sch Med, Dept Psychiat, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA

[8] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19014 USA

[9] Univ So Calif & Autism Speaks, Dept Biomed Engn, Los Angeles, CA 90089 USA

[10] Univ Washington, Dept Psychiat, Seattle, WA 98105 USA

[11] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA

[12] Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA

[13] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA

[14] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA

[15] Yale Univ, Dept Genet, New Haven, CT 06520 USA

[16] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA

[17] Univ Illinois, Inst Juvenile Res, Chicago, IL 60608 USA

[18] Univ Illinois, Dept Psychiat, Chicago, IL 60608 USA

[19] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA

[20] Univ Utah, Dept Psychiat, Salt Lake City, UT 84132 USA

[21] Univ Iowa, Dept Psychiat, Iowa City, IA USA

[22] Indiana Univ, Inst Psychiat Res, Indianapolis, IN 46202 USA

[23] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA

[24] Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN 37232 USA

[25] Vanderbilt Univ, Vanderbilt Kennedy Ctr, Nashville, TN 37232 USA

[26] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA

[27] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA

[28] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA

[29] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA

[30] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA

[31] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

来源：

NATURE | 2009年 / 459卷 / 7246期

基金：

英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; BIPOLAR DISORDER; FAMILIAL RISK; LINKAGE; LOCI; UNDERCONNECTIVITY; DISCONNECTION; EXPRESSION; IDENTIFICATION; CHROMOSOME;

D O I：

10.1038/nature07999

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)-two genes encoding neuronal cell-adhesion molecules-revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 x 10(-8), odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 x 10(-8) to 2.1 x 10(-10). Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.

引用

页码：528 / 533

页数：6

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