Individual common variants exert weak effects on the risk for autism spectrum disorders. - Inserm - Institut national de la santé et de la recherche médicale
Article Dans Une Revue Human Molecular Genetics Année : 2012

Individual common variants exert weak effects on the risk for autism spectrum disorders.

Richard Anney (1) , Lambertus Klei (2) , Dalila Pinto (3) , Joana Almeida (4) , Elena Bacchelli (5) , Gillian Baird (6) , Nadia Bolshakova (1) , Sven Bölte (7) , Patrick F. Bolton (8) , Thomas Bourgeron (9) , Sean Brennan (1) , Jessica Brian (10) , Jillian Casey (11) , Judith Conroy (11) , Catarina Correia (12, 13) , Christina Corsello (14) , Emily L. Crawford (15, 16) , Maretha de Jonge (17) , Richard Delorme (18, 19) , Eftichia Duketis (7) , Frederico Duque (4) , Annette Estes (20) , Penny Farrar (21) , Bridget A. Fernandez (22) , Susan E. Folstein (23, 24) , Eric Fombonne (25) , John Gilbert (24) , Christopher Gillberg (26) , Joseph T. Glessner (27) , Andrew Green (11) , Jonathan Green (28) , Stephen J. Guter (29) , Elizabeth A. Heron (1) , Richard Holt (21) , Jennifer L. Howe (3, 30) , Gillian Hughes (1) , Vanessa Hus (14) , Roberta Igliozzi (31) , Suma Jacob (29) , Graham P. Kenny (1) , Cecilia Kim (27) , Alexander Kolevzon (32) , Vlad Kustanovich (33) , Clara M. Lajonchere (33) , Janine A. Lamb (34) , Miriam Law-Smith (1) , Marion Leboyer (19, 35, 36) , Ann Le Couteur (37) , Bennett L. Leventhal (38) , Xiao-Qing Liu (30) , Frances Lombard (1) , Catherine Lord (14) , Linda Lotspeich (31) , Sabata C. Lund (15, 16) , Tiago R. Magalhaes (12, 13) , Carine Mantoulan (39) , Christopher J. Mcdougle (40) , Nadine M. Melhem (2) , Alison Merikangas (1) , Nancy J. Minshew (2) , Ghazala K. Mirza (21) , Jeff Munson (41) , Carolyn Noakes (10) , Gudrun Nygren (26) , Katerina Papanikolaou (42) , Alistair T. Pagnamenta (21) , Barbara Parrini (31) , Tara Paton (30) , Andrew Pickles (43) , David J. Posey (40) , Fritz Poustka (7) , Jiannis Ragoussis (21) , Regina Regan (11) , Wendy Roberts (10) , Kathryn Roeder (44) , Bernadette Roge (45) , Michael L. Rutter (46) , Sabine Schlitt (7) , Naisha Shah (11) , Val C. Sheffield (47) , Latha Soorya (32) , Inês Sousa (21) , Vera Stoppioni (48) , Nuala Sykes (21) , Raffaella Tancredi (31) , Ann P. Thompson (49) , Susanne Thomson (15, 16) , Ana Tryfon (32) , John Tsiantis (42) , Herman van Engeland (17) , John B. Vincent (50) , Fred Volkmar (51) , Jacob Vorstman (17) , Simon Wallace (52) , Kirsty Wing (21) , Kerstin Wittemeyer (52) , Shawn Wood (2) , Danielle Zurawiecki (32) , Lonnie Zwaigenbaum (53) , Anthony J. Bailey (52, 54) , Agatino Battaglia (31) , Rita M. Cantor (55) , Hilary Coon (56) , Michael L. Cuccaro (24) , Geraldine Dawson (57) , Sean Ennis (11) , Christine M. Freitag (7) , Daniel H. Geschwind (58) , Jonathan L. Haines (16) , Sabine M. Klauck (59) , William M. Mcmahon (56) , Elena Maestrini (5) , Judith Miller (56) , Anthony P. Monaco (21) , Stanley F. Nelson (55) , John I. Nurnberger (40) , Guiomar Oliveira (4) , Jeremy R. Parr (60) , Margaret A. Pericak-Vance (24) , Joseph Piven (61) , Gerard D. Schellenberg (62) , Stephen W. Scherer (3, 10, 30) , Astrid M. Vicente (12, 13) , Thomas H. Wassink (63) , Ellen M. Wijsman (64) , Catalina Betancur (65) , Joseph D. Buxbaum (32) , Edwin H. Cook (29) , Louise Gallagher (1) , Michael Gill (1) , Joachim Hallmayer (66) , Andrew D. Paterson (30, 3) , James S. Sutcliffe (15, 16) , Peter Szatmari (49) , Veronica J. Vieland (67) , Hakon Hakonarson (27, 68) , Bernie Devlin (2)
1 Division of Mental Health and Addiction
2 Department of Psychiatry [Pittsburgh]
3 The Centre for Applied Genomics, Toronto
4 UNDA - Unidade de Neurodesenvolvimento e Autismo
5 Department of Pharmacy and Biotechnology
6 Newcomen Centre
7 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy
8 Department of Child and Adolescent Psychiatry
9 Molecular and Cellular Neurobiology
10 Autism Research Unit
11 ACoRD - Academic Centre on Rare Diseases
12 INSA - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]
13 BioFIG
14 Autism and Communicative Disorders Centre
15 Department of Molecular Physiology & Biophysics and Psychiatry
16 Vanderbilt Brain Institute
17 Department of Psychiatry
18 Service de psychopathologie de l'enfant et de l'adolescent
19 IMRB - Institut Mondor de Recherche Biomédicale
20 Department of Speech and Hearing Sciences [Washington]
21 The Wellcome Trust Centre for Human Genetics [Oxford]
22 Disciplines of Genetics and Medicine
23 Department of Psychiatry
24 John P. Hussman Institute for Human Genomics
25 Research Unit on Children's Psychosocial Maladjustment
26 Department of Child and Adolescent Psychiatry
27 The Center for Applied Genomics
28 Manchester Academic Health Sciences Centre
29 Department of Disability and Human Development
30 Program in Genetics and Genomic Biology
31 Department of Psychiatry and Behavioral Sciences [Stanford]
32 Human Genetics Center
33 Autism Genetic Resource Exchange
34 Centre for Integrated Genomic Medical Research, Manchester
35 Service de psychiatrie
36 ENBREC - European Network of Bipolar Research Expert Centres
37 Department of Child and Adolescent Psychiatry
38 Department of Child and Adolescent Psychiatry
39 SPW-PRADORT - Centre de Référence du Syndrome de Prader-Willi [CHU Toulouse]
40 Department of Psychiatry
41 Department of Psychiatry and Behavioral Sciences
42 University Department of Child Psychiatry
43 Department of Medicine, Manchester
44 Department of Statistics
45 Octogone - Octogone Unité de Recherche Interdisciplinaire
46 Social, Genetic and Developmental Psychiatry Centre
47 Department of Pediatrics
48 Neuropsichiatria Infantile
49 Department of Psychiatry and Behavioural Neurosciences
50 Department of Psychiatry
51 Child Study Centre
52 Department of Psychiatry
53 Department of Pediatrics
54 SGDP - MRC Social, Genetic and Developmental Psychiatry Centre
55 Department of Human Genetics, Los Angeles
56 Department of Developmental Neuroscience
57 Autism Speaks and the Department of Psychiatry
58 Department of Neurology
59 Division of Molecular Genome Analysis
60 Institutes of Neuroscience and Health and Society
61 Carolina Institute for Developmental Disabilities
62 Pathology and Laboratory Medicine
63 Department of Psychiatry
64 Departments of Biostatistics and Medicine
65 Physiopathologie des Maladies du Système Nerveux Central
66 Stanford School of Medicine [Stanford]
67 Battelle Center for Mathematical Medicine
68 Department of Pediatrics
Gillian Baird
  • Fonction : Auteur
Thomas Bourgeron
Ana Tryfon
  • Fonction : Auteur
Fred Volkmar
  • Fonction : Auteur
Jacob Vorstman
  • Fonction : Auteur
  • PersonId : 879600

Résumé

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.

Domaines

Génétique
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Dates et versions

inserm-00723650 , version 1 (12-08-2012)

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Richard Anney, Lambertus Klei, Dalila Pinto, Joana Almeida, Elena Bacchelli, et al.. Individual common variants exert weak effects on the risk for autism spectrum disorders.. Human Molecular Genetics, 2012, 21 (21), pp.4781-92. ⟨10.1093/hmg/dds301⟩. ⟨inserm-00723650⟩
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