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

New CAR Research Sheds Light on

 

Universal Screening for Autism in Toddlers

TitleA genome-wide scan for common alleles affecting risk for autism.
Publication TypeJournal Article
Year of Publication2010
AuthorsAnney, 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
JournalHum Mol Genet
Volume19
Issue20
Pagination4072-82
Date Published2010 Oct 15
ISSN1460-2083
KeywordsAlleles, 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.

DOI10.1093/hmg/ddq307
Alternate JournalHum. Mol. Genet.
PubMed ID20663923
PubMed Central IDPMC2947401
Grant ListK01 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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