A genome-wide scan for common alleles affecting risk for autism

被引：439

作者：

Anney, Richard ^{[2
]}

Klei, Lambertus ^{[1
]}

Pinto, Dalila ^{[3
,4
,5
]}

Regan, Regina ^{[6
]}

Conroy, Judith ^{[6
]}

Magalhaes, Tiago R. ^{[7
,8
,9
]}

Correia, Catarina ^{[7
,8
,9
]}

Abrahams, Brett S. ^{[10
]}

Sykes, Nuala ^{[11
]}

Pagnamenta, Alistair T. ^{[11
]}

Almeida, Joana ^{[12
]}

Bacchelli, Elena ^{[13
]}

Bailey, Anthony J. ^{[14
]}

Baird, Gillian ^{[15
]}

Battaglia, Agatino ^{[16
]}

Berney, Tom ^{[17
]}

Bolshakova, Nadia ^{[2
]}

Boelte, Sven ^{[18
]}

Bolton, Patrick F. ^{[19
]}

Bourgeron, Thomas ^{[20
]}

Brennan, Sean ^{[2
]}

Brian, Jessica ^{[21
]}

Carson, Andrew R. ^{[3
,4
,5
]}

Casallo, Guillermo ^{[3
,4
,5
]}

Casey, Jillian ^{[6
]}

Chu, Su H. ^{[23
]}

Cochrane, Lynne ^{[2
]}

Corsello, Christina ^{[22
]}

Crawford, Emily L. ^{[24
,25
,26
]}

Crossett, Andrew ^{[23
]}

Dawson, Geraldine ^{[27
,28
]}

de Jonge, Maretha ^{[29
]}

Delorme, Richard ^{[30
]}

Drmic, Irene ^{[21
]}

Duketis, Eftichia ^{[18
]}

Duque, Frederico ^{[12
]}

Estes, Annette ^{[31
]}

Farrar, Penny ^{[11
]}

Fernandez, Bridget A. ^{[35
]}

Folstein, Susan E. ^{[36
]}

Fombonne, Eric ^{[37
]}

Freitag, Christine M. ^{[18
]}

Gilbert, John ^{[36
]}

Gillberg, Christopher ^{[38
]}

Glessner, Joseph T. ^{[39
]}

Goldberg, Jeremy ^{[40
]}

Green, Jonathan ^{[41
]}

Guter, Stephen J. ^{[42
]}

Hakonarson, Hakon ^{[39
,43
]}

Heron, Elizabeth A. ^{[2
]}

机构：

[1] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15232 USA

[2] Univ Dublin Trinity Coll, Sch Med, Dept Psychiat, Autism Genet Grp, Dublin 8, Ireland

[3] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1L7, Canada

[4] Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON M5G 1L7, Canada

[5] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1L7, Canada

[6] Univ Coll Dublin, Sch Med & Med Sci, Dublin 4, Ireland

[7] Inst Nacl Saude Dr Ricardo Jorge, P-1649016 Lisbon, Portugal

[8] Inst Gulbenkian Ciencias, P-1649016 Lisbon, Portugal

[9] BioFIG Ctr Biodivers Funct & Integrat Genom, P-1749016 Lisbon, Portugal

[10] Univ Calif Los Angeles, Dept Neurol, Sch Med, Los Angeles, CA 90095 USA

[11] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[12] Hosp Pediat Coimbra, P-3000076 Coimbra, Portugal

[13] Univ Bologna, Dept Biol, I-40126 Bologna, Italy

[14] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England

[15] Guys Hosp, Newcomen Ctr, London SE1 9RT, England

[16] Stella Maris Inst Child & Adolescent Neuropsychia, I-56128 Pisa, Italy

[17] Newcastle Univ, Sir James Spence Inst, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England

[18] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60528 Frankfurt, Germany

[19] Inst Psychiat, Dept Child & Adolescent Psychiat, London SE5 8AF, England

[20] Univ Paris 07, Inst Pasteur, CNRS URA 2182, Fdn FondaMental, F-75015 Paris, France

[21] Univ Toronto, Autism Res Unit, Hosp Sick Children & Bloorview Kids Rehabil, Toronto, ON M5G 1Z8, Canada

[22] Univ Michigan, Autism & Communicat Disorders Ctr, Ann Arbor, MI 48109 USA

[23] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA

[24] Vanderbilt Univ, Dept Mol Physiol & Biophys, Vanderbilt Kennedy Ctr, Nashville, TN 37232 USA

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

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

[27] Autism Speaks, New York, NY 10016 USA

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

[29] Univ Med Ctr, Dept Child Psychiat, NL-3508 GA Utrecht, Netherlands

[30] Hop Robert Debre, APHP, F-75019 Paris, France

[31] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA

[32] Univ Washington, Dept Med, Seattle, WA 98195 USA

[33] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA

[34] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[35] Mem Univ Newfoundland, Disciplines Genet & Med, St John, NF A1B 3V6, Canada

[36] Univ Miami, John P Hussman Inst Human Genom, Miami, FL 33101 USA

[37] McGill Univ, Div Psychiat, Montreal, PQ H3A 1A1, Canada

[38] Univ Gothenburg, Dept Child & Adolescent Psychiat, S-41345 Gothenburg, Sweden

[39] Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Genom, Philadelphia, PA 19104 USA

[40] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON L8N 3Z5, Canada

[41] Booth Hall Childrens Hosp, Acad Dept Child Psychiat, Manchester M9 7AA, Lancs, England

[42] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60608 USA

[43] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA

[44] German Canc Res Ctr, Div Mol Genome Anal, D-69120 Heidelberg, Germany

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

[46] Autism Speaks, Autism Genet Resource Exchange, Los Angeles, CA 90036 USA

[47] Univ Manchester, Ctr Integrated Genom Med Res, Manchester M13 9PT, Lancs, England

[48] Univ Paris 12, Grp Hosp Henri Mondor Albert Chenevier, AP HP, INSERM U995,Dept Psychiat,Fdn FondaMental, F-94000 Creteil, France

[49] Nathan Kline Inst Psychiat Res NKI, Orangeburg, NY 10962 USA

[50] NYU, Dept Child & Adolescent Psychiat, New York, NY 10016 USA

来源：

HUMAN MOLECULAR GENETICS | 2010年 / 19卷 / 20期

基金：

美国国家卫生研究院; 英国医学研究理事会; 加拿大创新基金会; 英国惠康基金;

关键词：

COPY NUMBER VARIATION; SPECTRUM DISORDERS; GENETIC ARCHITECTURE; PTEN MUTATIONS; ASSOCIATION; REVEALS; LINKAGE; SCHIZOPHRENIA; INDIVIDUALS; PREVALENCE;

D O I：

10.1093/hmg/ddq307

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：

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 x 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 x 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

引用

页码：4072 / 4082

页数：11

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