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Individual common variants exert weak effects on the risk for autism spectrum disorders.

Publication ,  Journal Article
Anney, R; Klei, L; Pinto, D; Almeida, J; Bacchelli, E; Baird, G; Bolshakova, N; Bölte, S; Bolton, PF; Bourgeron, T; Brennan, S; Brian, J ...
Published in: Hum Mol Genet
November 1, 2012

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

November 1, 2012

Volume

21

Issue

21

Start / End Page

4781 / 4792

Location

England

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Nerve Tissue Proteins
  • Membrane Proteins
  • Male
  • Language Development
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetics & Heredity
 

Citation

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Anney, R., Klei, L., Pinto, D., Almeida, J., Bacchelli, E., Baird, G., … Devlin, B. (2012). Individual common variants exert weak effects on the risk for autism spectrum disorders. Hum Mol Genet, 21(21), 4781–4792. https://doi.org/10.1093/hmg/dds301
Anney, Richard, Lambertus Klei, Dalila Pinto, Joana Almeida, Elena Bacchelli, Gillian Baird, Nadia Bolshakova, et al. “Individual common variants exert weak effects on the risk for autism spectrum disorders.Hum Mol Genet 21, no. 21 (November 1, 2012): 4781–92. https://doi.org/10.1093/hmg/dds301.
Anney R, Klei L, Pinto D, Almeida J, Bacchelli E, Baird G, et al. Individual common variants exert weak effects on the risk for autism spectrum disorders. Hum Mol Genet. 2012 Nov 1;21(21):4781–92.
Anney, Richard, et al. “Individual common variants exert weak effects on the risk for autism spectrum disorders.Hum Mol Genet, vol. 21, no. 21, Nov. 2012, pp. 4781–92. Pubmed, doi:10.1093/hmg/dds301.
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 X-Q, 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 JAS, 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, Haines JL, Klauck SM, McMahon WM, Maestrini E, Miller J, Monaco AP, Nelson SF, Nurnberger JI, Oliveira G, Parr JR, Pericak-Vance MA, Piven J, Schellenberg GD, Scherer SW, Vicente AM, Wassink TH, Wijsman EM, Betancur C, Buxbaum JD, Cook EH, Gallagher L, Gill M, Hallmayer J, Paterson AD, Sutcliffe JS, Szatmari P, Vieland VJ, Hakonarson H, Devlin B. Individual common variants exert weak effects on the risk for autism spectrum disorders. Hum Mol Genet. 2012 Nov 1;21(21):4781–4792.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

November 1, 2012

Volume

21

Issue

21

Start / End Page

4781 / 4792

Location

England

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Nerve Tissue Proteins
  • Membrane Proteins
  • Male
  • Language Development
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetics & Heredity