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

2010; Oxford University Press; Volume: 19; Issue: 20 Linguagem: Inglês

10.1093/hmg/ddq307

1460-2083

Richard Anney, Lambertus Klei, Dalila Pinto, Regina Regan, Jennifer Conroy, Tiago R. Magalhães, Catarina Correia, Brett S. Abrahams, N. Sykes, A. T. Pagnamenta, J.-P. de Almeida, Elena Bacchelli, Anthony Bailey, Gillian Baird, Agatino Battaglia, T. P. Berney, Nadia Bolshakova, Sven Bölte, P. F. Bolton, Thomas Bourgeron, S. Brennan, Jessica Brian, A. R. Carson, Guillermo Casallo, Jillian P. Casey, Su H. Chu, Lynne Cochrane, Christina Corsello, E. L. Crawford, A. Crossett, Géraldine Dawson, Maretha Jonge, Richard Delorme, Irene Drmic, Eftichia Duketis, Frederico Duque, Annette Estes, Penny Farrar, Bridget A. Fernandez, Susan E. Folstein, Éric Fombonne, Christine M. Freitag, James Gilbert, Christopher Gillberg, Joseph Glessner, Joel O. Goldberg, Jonathan Green, Stephen J. Guter, Hákon Hákonarson, Elizabeth A. Heron, Matthew Hill, Richard Holt, Jennifer Howe, Gillian Hughes, Vanessa Hus, Roberta Igliozzi, C. Kim, Sabine M. Klauck, Alexander Kolevzon, Olena Korvatska, Vlad Kustanovich, Clara Lajonchere, Janine A. Lamb, Magdalena Laskawiec, Marion Leboyer, Ann Le Couteur, Bennett Leventhal, A. C. Lionel, Xiaoqing Liu, Catherine Lord, Linda Lotspeich, Sabata C. Lund, Elena Maestrini, William J. Mahoney, Carine Mantoulan, Christian R. Marshall, Helen McConachie, Christopher J. McDougle, Jane McGrath, William M. McMahon, Nadine Melhem, Alison Merikangas, Ohsuke Migita, Nancy J. Minshew, Ghazala Mirza, Jeff Munson, Stanley F. Nelson, C. Noakes, Abdul Noor, Gudrun Nygren, Guiomar Oliveira, Κaterina Papanikolaou, Jeremy Parr, Barbara Parrini, Tara Paton, Andrew Pickles, Joseph Piven, David J. Posey, Annemarie Poustka, Fritz Poustka, Aparna Prasad, Jiannis Ragoussis, Katy Renshaw, Jessica Rickaby, Wendy Roberts, Kathryn Roeder, Bernadette Rogé, Michael Rutter, Laura J. Bierut, John P. Rice, Jeff Salt, Katherine Sansom, Daisuke Sato, Ricardo Segurado, L. Senman, Naisha Shah, Val C. Sheffield, Latha Soorya, Inês Sousa, Vera Stoppioni, Christina P. Strawbridge, Raffaella Tancredi, Katherine E. Tansey, Bhooma Thiruvahindrapduram, A. P. Thompson, Susan Thomson, Ana Tryfon, John Tsiantis, Hermán van Engeland, John B. Vincent, Fred R. Volkmar, Simon Wallace, Kai Wang, Zhonghua Wang, Thomas H. Wassink, Kirsty Wing, Kerstin Wittemeyer, S. Wood, Brian L. Yaspan, Danielle Zurawiecki, Lonnie Zwaigenbaum, Catalina Betancur, Joseph D. Buxbaum, Rita M. Cantor, Edwin H. Cook, Hilary Coon, Michael L. Cuccaro, Louise Gallagher, Daniel H. Geschwind, Michael Gill, J.L. Haines, Judith Miller, Anthony P. Monaco, John I. Nürnberger, Andrew D. Paterson, Margaret A. Pericak‐Vance, Gerard D. Schellenberg, Stephen W. Scherer, James S. Sutcliffe, Peter Szatmari, Astrid M. Vicente, Veronica J. Vieland, Ellen M. Wijsman, Bernie Devlin, Sean Ennis, Joachim Hallmayer,

Genetics and Neurodevelopmental Disorders

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 × 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 × 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.