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 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 Crawford 15, 16 Maretha De Jonge 17 Richard Delorme 18, 19 Eftichia Duketis 7 Frederico Duque 4 Annette Estes 20 Penny Farrar 21 Bridget Fernandez 22 Susan Folstein 23, 24 Eric Fombonne 25 John Gilbert 24 Christopher Gillberg 26 Joseph Glessner 27 Andrew Green 11 Jonathan Green 28 Stephen Guter 29 Elizabeth Heron 1 Richard Holt 21 Jennifer Howe 3, 30 Gillian Hughes 1 Vanessa Hus 14 Roberta Igliozzi 31 Suma Jacob 29 Graham Kenny 1 Cecilia Kim 27 Alexander Kolevzon 32 Vlad Kustanovich 33 Clara Lajonchere 33 Janine Lamb 34 Miriam Law-Smith 1 Marion Leboyer 19, 35, 36 Ann Le Couteur 37 Bennett Leventhal 38 Xiao-Qing Liu 30 Frances Lombard 1 Catherine Lord 14 Linda Lotspeich 39 Sabata Lund 15, 16 Tiago Magalhaes 12, 13 Carine Mantoulan 40 Christopher Mcdougle 41 Nadine Melhem 2 Alison Merikangas 1 Nancy Minshew 2 Ghazala Mirza 21 Jeff Munson 42 Carolyn Noakes 10 Gudrun Nygren 26 Katerina Papanikolaou 43 Alistair Pagnamenta 21 Barbara Parrini 31 Tara Paton 30 Andrew Pickles 44 David Posey 41 Fritz Poustka 7 Jiannis Ragoussis 21 Regina Regan 11 Wendy Roberts 10 Kathryn Roeder 45 Bernadette Roge 46 Michael Rutter 47 Sabine Schlitt 7 Naisha Shah 11 Val Sheffield 48 Latha Soorya 32 Inês Sousa 21 Vera Stoppioni 49 Nuala Sykes 21 Raffaella Tancredi 31 Ann Thompson 50 Susanne Thomson 15, 16 Ana Tryfon 32 John Tsiantis 43 Herman Van Engeland 17 John Vincent 51 Fred Volkmar 52 Jacob Vorstman 17 Simon Wallace 53 Kirsty Wing 21 Kerstin Wittemeyer 53 Shawn Wood 2 Danielle Zurawiecki 32 Lonnie Zwaigenbaum 54 Anthony Bailey 53, 55 Agatino Battaglia 31 Rita Cantor 56 Hilary Coon 57 Michael Cuccaro 24 Geraldine Dawson 58 Sean Ennis 11 Christine Freitag 7 Daniel Geschwind 59 Jonathan Haines 16 Sabine Klauck 60 William Mcmahon 57 Elena Maestrini 5 Judith Miller 57 Anthony Monaco 21 Stanley Nelson 56 John Nurnberger 41 Guiomar Oliveira 4 Jeremy Parr 61 Margaret Pericak-Vance 24 Joseph Piven 62 Gerard Schellenberg 63 Stephen Scherer 3, 10, 30 Astrid Vicente 12, 13 Thomas Wassink 64 Ellen Wijsman 65 Catalina Betancur 66 Joseph Buxbaum 32 Edwin Cook 29 Louise Gallagher 1 Michael Gill 1 Joachim Hallmayer 67 Andrew Paterson 30, 3 James Sutcliffe 15, 16 Peter Szatmari 50 Veronica Vieland 68 Hakon Hakonarson 27, 69 Bernie Devlin 2, *
* Auteur correspondant
Abstract : 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.
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Article dans une revue
Human Molecular Genetics, Oxford University Press (OUP), 2012, 21 (21), pp.4781-92. 〈10.1093/hmg/dds301〉
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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, Oxford University Press (OUP), 2012, 21 (21), pp.4781-92. 〈10.1093/hmg/dds301〉. 〈inserm-00723650〉

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