Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Oct 15;19(20):4072-82.
doi: 10.1093/hmg/ddq307. Epub 2010 Jul 27.

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

Richard Anney  1 , 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 Bourgeron, Sean 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 Jr, 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
Affiliations

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

Richard Anney et al. Hum Mol Genet. .

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Association results, presented as the −log(base 10) of the P-values, for an intronic region of MACROD2 (20p12.1). The panels show the combinations of two diagnostic levels, strict versus spectrum and any versus European ancestry of the subjects. Recombination rates were calculated using Release 22 of the HapMap CEU Panel.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Genetics and genomics of autism spectrum disorder: embracing complexity.
    De Rubeis S, Buxbaum JD. De Rubeis S, et al. Hum Mol Genet. 2015 Oct 15;24(R1):R24-31. doi: 10.1093/hmg/ddv273. Epub 2015 Jul 17. Hum Mol Genet. 2015. PMID: 26188008 Free PMC article. Review.
  • Social responsiveness, an autism endophenotype: genomewide significant linkage to two regions on chromosome 8.
    Lowe JK, Werling DM, Constantino JN, Cantor RM, Geschwind DH. Lowe JK, et al. Am J Psychiatry. 2015 Mar 1;172(3):266-75. doi: 10.1176/appi.ajp.2014.14050576. Epub 2014 Nov 7. Am J Psychiatry. 2015. PMID: 25727539 Free PMC article.
  • Individual common variants exert weak effects on the risk for autism spectrum disorders.
    Anney R, Klei L, Pinto D, Almeida J, Bacchelli E, Baird G, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Casey J, Conroy J, Correia C, Corsello C, Crawford EL, de Jonge M, Delorme R, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Gilbert J, Gillberg C, Glessner JT, Green A, Green J, Guter SJ, Heron EA, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Jacob S, Kenny GP, Kim C, Kolevzon A, Kustanovich V, Lajonchere CM, Lamb JA, Law-Smith M, Leboyer M, Le Couteur A, Leventhal BL, Liu XQ, Lombard F, Lord C, Lotspeich L, Lund SC, Magalhaes TR, Mantoulan C, McDougle CJ, Melhem NM, Merikangas A, Minshew NJ, Mirza GK, Munson J, Noakes C, Nygren G, Papanikolaou K, Pagnamenta AT, Parrini B, Paton T, Pickles A, Posey DJ, Poustka F, Ragoussis J, Regan R, Roberts W, Roeder K, Roge B, Rutter ML, Schlitt S, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Sykes N, Tancredi R, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Vorstman JA, Wallace S, Wing K, Wittemeyer K, Wood S, Zurawiecki D, Zwaigenbaum L, Bailey AJ, Battaglia A, Cantor RM, Coon H, Cuccaro ML, Dawson G, Ennis S, Freitag CM, Geschwind DH, Hai… See abstract for full author list ➔ Anney R, et al. Hum Mol Genet. 2012 Nov 1;21(21):4781-92. doi: 10.1093/hmg/dds301. Epub 2012 Jul 26. Hum Mol Genet. 2012. PMID: 22843504 Free PMC article.
  • The first Malay database toward the ethnic-specific target molecular variation.
    Halim-Fikri H, Etemad A, Abdul Latif AZ, Merican AF, Baig AA, Annuar AA, Ismail E, Salahshourifar I, Liza-Sharmini AT, Ramli M, Shah MI, Johan MF, Hassan NN, Abdul-Aziz NM, Mohd Noor NH, Nur-Shafawati AR, Hassan R, Bahar R, Zain RB, Yusoff SM, Yusoff S, Tan SG, Thong MK, Wan-Isa H, Abdullah WZ, Mohamed Z, Abdul Latiff Z, Zilfalil BA; members of the Malaysian Node of the Human Variome Project. Halim-Fikri H, et al. BMC Res Notes. 2015 Apr 30;8:176. doi: 10.1186/s13104-015-1123-y. BMC Res Notes. 2015. PMID: 25925844 Free PMC article.
  • Personalized medicine: caught between hope, hype and the real world.
    Dammann M, Weber F. Dammann M, et al. Clinics (Sao Paulo). 2012;67 Suppl 1(Suppl 1):91-7. doi: 10.6061/clinics/2012(sup01)16. Clinics (Sao Paulo). 2012. PMID: 22584712 Free PMC article. Review.
See all "Cited by" articles

References

    1. Cook E.H., Jr, Scherer S.W. Copy-number variations associated with neuropsychiatric conditions. Nature. 2008;455:919–923. - PubMed
    1. Lord C., Rutter M., Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J. Autism Dev. Disord. 1994;24:659–685. doi:10.1007/BF02172145. - DOI - PubMed
    1. Lord C., Risi S., Lambrecht L., Cook E.H., Jr, Leventhal B.L., DiLavore P.C., Pickles A., Rutter M. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J. Autism Dev. Disord. 2000;30:205–223. doi:10.1023/A:1005592401947. - DOI - PubMed
    1. Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr. Res. 2009;65:591–598. doi:10.1203/PDR.0b013e31819e7203. - DOI - PubMed
    1. Fernell E., Gillberg C. Autism spectrum disorder diagnoses in Stockholm preschoolers. Res. Dev. Disabil. 2010;31:680–685. - PubMed

Publication types

Grants and funding