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

Richard Anney, Lambertus Klei, Dalila Pinto, Regina Regan, Judith Conroy, Tiago R. Magalhaes, Catarina Correia, Brett S. Abrahams, Nuala Sykes, Alistair T. Pagnamenta, Joana Almeida, Elena Bacchelli, Anthony J. Bailey, Gillian Baird, Agatino Battaglia, Tom Berney, Nadia Bolshakova, Sven Bölte, Patrick F. Bolton, Thomas BourgeronSean Brennan, Jessica Brian, Andrew R. Carson, Guillermo Casallo, Jillian Casey, Su H. Chu, Lynne Cochrane, Christina Corsello, Emily L. Crawford, Andrew Crossett, Geraldine Dawson, Maretha de Jonge, Richard Delorme, Irene Drmic, Eftichia Duketis, Frederico Duque, Annette Estes, Penny Farrar, Bridget A. Fernandez, Susan E. Folstein, Eric Fombonne, Christine M. Freitag, John Gilbert, Christopher Gillberg, Joseph T. Glessner, Jeremy Goldberg, Jonathan Green, Stephen J. Guter, Hakon Hakonarson, Elizabeth A. Heron, Matthew Hill, Richard Holt, Jennifer L. Howe, Gillian Hughes, Vanessa Hus, Roberta Igliozzi, Cecilia Kim, Sabine M. Klauck, Alexander Kolevzon, Olena Korvatska, Vlad Kustanovich, Clara M. Lajonchere, Janine A. Lamb, Magdalena Laskawiec, Marion Leboyer, Ann Le Couteur, Bennett L. Leventhal, Anath C. Lionel, Xiao Qing Liu, Catherine Lord, Linda Lotspeich, Sabata C. Lund, Elena Maestrini, William Mahoney, Carine Mantoulan, Christian R. Marshall, Helen McConachie, Christopher J. McDougle, Jane McGrath, William M. McMahon, Nadine M. Melhem, Alison Merikangas, Ohsuke Migita, Nancy J. Minshew, Ghazala K. Mirza, Jeff Munson, Stanley F. Nelson, Carolyn Noakes, Abdul Noor, Gudrun Nygren, Guiomar Oliveira, Katerina Papanikolaou, Jeremy R. 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 Roge, Michael L. Rutter, Laura J. Bierut, John P. Rice, Jeff Salt, Katherine Sansom, Daisuke Sato, Ricardo Segurado, Lili Senman, Naisha Shah, Val C. Sheffield, Latha Soorya, Inês Sousa, Vera Stoppioni, Christina Strawbridge, Raffaella Tancredi, Katherine Tansey, Bhooma Thiruvahindrapduram, Ann P. Thompson, Susanne Thomson, Ana Tryfon, John Tsiantis, Herman van Engeland, John B. Vincent, Fred Volkmar, Simon Wallace, Kai Wang, Zhouzhi Wang, Thomas H. Wassink, Kirsty Wing, Kerstin Wittemeyer, Shawn 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, Jonathan L. Haines, Judith Miller, Anthony P. Monaco, John I. Nurnberger, 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

Research output: Contribution to journalArticle

405 Scopus citations

Abstract

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 3 10-28. 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 × 10-28 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.

Original languageEnglish (US)
Pages (from-to)4072-4082
Number of pages11
JournalHuman molecular genetics
Volume19
Issue number20
DOIs
StatePublished - Jul 27 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Anney, R., Klei, L., Pinto, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., Sykes, N., Pagnamenta, A. T., Almeida, J., Bacchelli, E., Bailey, A. J., Baird, G., Battaglia, A., Berney, T., Bolshakova, N., Bölte, S., Bolton, P. F., ... Hallmayer, J. (2010). A genome-wide scan for common alleles affecting risk for autism. Human molecular genetics, 19(20), 4072-4082. https://doi.org/10.1093/hmg/ddq307