Title | A genome-wide scan for common alleles affecting risk for autism. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Anney, R, Klei, L, Pinto, D, Regan, R, Conroy, J, Magalhaes, TR, Correia, C, Abrahams, BS, Sykes, N, Pagnamenta, AT, Almeida, J, Bacchelli, E, Bailey, AJ, Baird, G, Battaglia, A, Berney, T, Bolshakova, N, Bölte, S, Bolton, PF, Bourgeron, T, Brennan, S, Brian, J, Carson, AR, Casallo, G, Casey, J, Chu, SH, Cochrane, L, Corsello, C, Crawford, EL, Crossett, A, Dawson, G, de Jonge, M, Delorme, R, Drmic, I, Duketis, E, Duque, F, Estes, A, Farrar, P, Fernandez, BA, Folstein, SE, Fombonne, E, Freitag, CM, Gilbert, J, Gillberg, C, Glessner, JT, Goldberg, J, Green, J, Guter, SJ, Hakonarson, H, Heron, EA, Hill, M, Holt, R, Howe, JL, Hughes, G, Hus, V, Igliozzi, R, Kim, C, Klauck, SM, Kolevzon, A, Korvatska, O, Kustanovich, V, Lajonchere, CM, Lamb, JA, Laskawiec, M, Leboyer, M, Le Couteur, A, Leventhal, BL, Lionel, AC, Liu, X-Q, Lord, C, Lotspeich, L, Lund, SC, Maestrini, E, Mahoney, W, Mantoulan, C, Marshall, CR, McConachie, H, McDougle, CJ, McGrath, J, McMahon, WM, Melhem, NM, Merikangas, A, Migita, O, Minshew, NJ, Mirza, GK, Munson, J, Nelson, SF, Noakes, C, Noor, A, Nygren, G, Oliveira, G, Papanikolaou, K, Parr, JR, Parrini, B, Paton, T, Pickles, A, Piven, J, Posey, DJ, Poustka, A, Poustka, F, Prasad, A, Ragoussis, J, Renshaw, K, Rickaby, J, Roberts, W, Roeder, K, Rogé, B, Rutter, ML, Bierut, LJ, Rice, JP, Salt, J, Sansom, K, Sato, D, Segurado, R, Senman, L, Shah, N, Sheffield, VC, Soorya, L, Sousa, I, Stoppioni, V, Strawbridge, C, Tancredi, R, Tansey, K, Thiruvahindrapduram, B, Thompson, AP, Thomson, S, Tryfon, A, Tsiantis, J, van Engeland, H, Vincent, JB, Volkmar, F, Wallace, S, Wang, K, Wang, Z, Wassink, TH, Wing, K, Wittemeyer, K, Wood, S, Yaspan, BL, Zurawiecki, D, Zwaigenbaum, L, Betancur, C, Buxbaum, JD, Cantor, RM, Cook, EH, Coon, H, Cuccaro, ML, Gallagher, L, Geschwind, DH, Gill, M, Haines, JL, Miller, J, Monaco, AP, Nurnberger, JI, Paterson, AD, Pericak-Vance, MA, Schellenberg, GD, Scherer, SW, Sutcliffe, JS, Szatmari, P, Vicente, AM, Vieland, VJ, Wijsman, EM, Devlin, B, Ennis, S, Hallmayer, J |
Journal | Hum Mol Genet |
Volume | 19 |
Issue | 20 |
Pagination | 4072-82 |
Date Published | 2010 Oct 15 |
ISSN | 1460-2083 |
Keywords | Alleles, Autistic Disorder, Databases, Genetic, DNA Copy Number Variations, European Continental Ancestry Group, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Risk Factors |
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. |
DOI | 10.1093/hmg/ddq307 |
Alternate Journal | Hum. Mol. Genet. |
PubMed ID | 20663923 |
PubMed Central ID | PMC2947401 |
Grant List | K01 MH077930 / MH / NIMH NIH HHS / United States P50 HD055782 / HD / NICHD NIH HHS / United States MH066673 / MH / NIMH NIH HHS / United States U19 HD035469-10 / HD / NICHD NIH HHS / United States U01 HG004422-02 / HG / NHGRI NIH HHS / United States NS049261 / NS / NINDS NIH HHS / United States MH077930 / MH / NIMH NIH HHS / United States U10 AA008401 / AA / NIAAA NIH HHS / United States U19 HD035469-09 / HD / NICHD NIH HHS / United States MH55284 / MH / NIMH NIH HHS / United States MH080647 / MH / NIMH NIH HHS / United States MH061009 / MH / NIMH NIH HHS / United States HD055782 / HD / NICHD NIH HHS / United States U19 HD035469 / HD / NICHD NIH HHS / United States MH081754 / MH / NIMH NIH HHS / United States T32 MH065215 / MH / NIMH NIH HHS / United States U19 HD035469-06 / HD / NICHD NIH HHS / United States MH66766 / MH / NIMH NIH HHS / United States MH52708 / MH / NIMH NIH HHS / United States R01 MH057881 / MH / NIMH NIH HHS / United States NS042165 / NS / NINDS NIH HHS / United States AS7462 / / Autism Speaks / United States / / Canadian Institutes of Health Research / Canada U01 HG004422 / HG / NHGRI NIH HHS / United States R01 DA019963-02 / DA / NIDA NIH HHS / United States P50 HD055751 / HD / NICHD NIH HHS / United States R01 DA019963 / DA / NIDA NIH HHS / United States U01 HG004438 / HG / NHGRI NIH HHS / United States U01 HG004446 / HG / NHGRI NIH HHS / United States HD055784 / HD / NICHD NIH HHS / United States / / Howard Hughes Medical Institute / United States MH057881 / MH / NIMH NIH HHS / United States MH06359 / MH / NIMH NIH HHS / United States R01 DA019963-01A2 / DA / NIDA NIH HHS / United States P01 CA089392 / CA / NCI NIH HHS / United States G0601030 / / Medical Research Council / United Kingdom R01 DA019963-03 / DA / NIDA NIH HHS / United States 075491/Z/04 UK / / Wellcome Trust / United Kingdom NS026630 / NS / NINDS NIH HHS / United States R01 DA013423 / DA / NIDA NIH HHS / United States HD35465 / HD / NICHD NIH HHS / United States P50 HD055751-03 / HD / NICHD NIH HHS / United States U19 HD035469-08 / HD / NICHD NIH HHS / United States U19 HD035469-07 / HD / NICHD NIH HHS / United States HD055751 / HD / NICHD NIH HHS / United States |
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