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PMID: 20663923 Published · ppublish English

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

Human molecular genetics ·Vol. 19 ·No. 20 ·2011-03-01

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

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 × 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.

Article Info
Journal
Human molecular genetics
Abbr.
Hum Mol Genet
Published
2011-03-01
Indexed
2010-09-30
Updated
2016-11-22
Language
English
Country/Region
England
NLM ID
9208958
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