Common genetic variants on 5p14.1 associate with autism spectrum disorders.

New CAR Research Sheds Light on

 

Universal Screening for Autism in Toddlers

TitleCommon genetic variants on 5p14.1 associate with autism spectrum disorders.
Publication TypeJournal Article
Year of Publication2009
AuthorsWang, K, Zhang, H, Ma, D, Bućan, M, Glessner, JT, Abrahams, BS, Salyakina, D, Imielinski, M, Bradfield, JP, Sleiman, PMA, Kim, CE, Hou, C, Frackelton, E, Chiavacci, R, Takahashi, N, Sakurai, T, Rappaport, E, Lajonchere, CM, Munson, J, Estes, A, Korvatska, O, Piven, J, Sonnenblick, LI, Retuerto, AIAlvarez, Herman, EI, Dong, H, Hutman, T, Sigman, M, Ozonoff, S, Klin, A, Owley, T, Sweeney, JA, Brune, CW, Cantor, RM, Bernier, R, Gilbert, JR, Cuccaro, ML, McMahon, WM, Miller, J, State, MW, Wassink, TH, Coon, H, Levy, SE, Schultz, RT, Nurnberger, JI, Haines, JL, Sutcliffe, JS, Cook, EH, Minshew, NJ, Buxbaum, JD, Dawson, G, Grant, SFA, Geschwind, DH, Pericak-Vance, MA, Schellenberg, GD, Hakonarson, H
JournalNature
Volume459
Issue7246
Pagination528-33
Date Published2009 May 28
ISSN1476-4687
KeywordsAutistic Disorder, Brain, Cadherins, Case-Control Studies, Cell Adhesion, Cell Adhesion Molecules, Neuronal, Chromosomes, Human, Pair 5, Cohort Studies, Genetic Markers, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Reproducibility of Results
Abstract

Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)-two genes encoding neuronal cell-adhesion molecules-revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 x 10(-8), odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 x 10(-8) to 2.1 x 10(-10). Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.

DOI10.1038/nature07999
Alternate JournalNature
PubMed ID19404256
PubMed Central IDPMC2943511
Grant ListR01 MH064547-05 / MH / NIMH NIH HHS / United States
P50 HD055782 / HD / NICHD NIH HHS / United States
MH64547 / MH / NIMH NIH HHS / United States
U24 MH081810 / MH / NIMH NIH HHS / United States
MH0666730 / MH / NIMH NIH HHS / United States
P50 HD055782-01 / HD / NICHD NIH HHS / United States
M01-RR00064 / RR / NCRR NIH HHS / United States
P50 HD055784-020002 / HD / NICHD NIH HHS / United States
R01 NS049261 / NS / NINDS NIH HHS / United States
NS049261 / NS / NINDS NIH HHS / United States
P01 NS026630 / NS / NINDS NIH HHS / United States
N01-HD-4-3383 / HD / NICHD NIH HHS / United States
R01 MH081754-01 / MH / NIMH NIH HHS / United States
P50 HD055784-01 / HD / NICHD NIH HHS / United States
MH080647 / MH / NIMH NIH HHS / United States
MH061009 / MH / NIMH NIH HHS / United States
R01 MH061009 / MH / NIMH NIH HHS / United States
MH081754 / MH / NIMH NIH HHS / United States
R01 MH081754-02 / MH / NIMH NIH HHS / United States
UL1 RR024134-01 / RR / NCRR NIH HHS / United States
R01 NS049261-01A2 / NS / NINDS NIH HHS / United States
/ / Medical Research Council / United Kingdom
1U24MH081810 / MH / NIMH NIH HHS / United States
P50 HD055784-010002 / HD / NICHD NIH HHS / United States
NS26630 / NS / NINDS NIH HHS / United States
R01 MH061009-01A1 / MH / NIMH NIH HHS / United States
R01 MH068398 / MH / NIMH NIH HHS / United States
R01 MH064547-01S1 / MH / NIMH NIH HHS / United States
R01 MH069359-01A2 / MH / NIMH NIH HHS / United States
N01-HD-4-3368 / HD / NICHD NIH HHS / United States
R01 NS036768-06 / NS / NINDS NIH HHS / United States
R01 MH080647-11 / MH / NIMH NIH HHS / United States
R01 NS036768 / NS / NINDS NIH HHS / United States
P50 HD055748 / HD / NICHD NIH HHS / United States
R01 MH064547-03 / MH / NIMH NIH HHS / United States
R01 MH064547-02 / MH / NIMH NIH HHS / United States
P50 HD055751 / HD / NICHD NIH HHS / United States
P50 HD055784 / HD / NICHD NIH HHS / United States
P50 HD055751-01 / HD / NICHD NIH HHS / United States
U54 MH066673-01A10001 / MH / NIMH NIH HHS / United States
R01 MH064547 / MH / NIMH NIH HHS / United States
R01 MH080647 / MH / NIMH NIH HHS / United States
HD055784 / HD / NICHD NIH HHS / United States
R01 MH081754 / MH / NIMH NIH HHS / United States
P50 HD055784-030002 / HD / NICHD NIH HHS / United States
NS36768 / NS / NINDS NIH HHS / United States
P01 NS026630-109001 / NS / NINDS NIH HHS / United States
R01 MH069359 / MH / NIMH NIH HHS / United States
UL1-RR024134-03 / RR / NCRR NIH HHS / United States
R01 MH064547-01 / MH / NIMH NIH HHS / United States
R01 MH064547-02S1 / MH / NIMH NIH HHS / United States
HD055782-01 / HD / NICHD NIH HHS / United States
M01 RR000064 / RR / NCRR NIH HHS / United States
MH69359 / MH / NIMH NIH HHS / United States
R01 MH064547-04 / MH / NIMH NIH HHS / United States
U54 MH066673 / MH / NIMH NIH HHS / United States
UL1 RR024134 / RR / NCRR NIH HHS / United States
HD055751 / HD / NICHD NIH HHS / United States
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