Common genetic variants on 5p14.1 associate with autism spectrum disorders by Wang Kai, Zhang Haitao, Ma Deqiong, Bucan Maja, Glessner Joseph T, Abrahams Brett S, Salyakina Daria, Imielinski Marcin, Bradfield Jonathan P, Sleiman Patrick M A, Kim Cecilia E, Hou Cuiping, Frackelton Edward, Chiavacci Rosetta, Takahashi Nagahide, Sakurai Takeshi, Rappaport Eric, Lajonchere Clara M, Munson Jeffrey, Estes Annette, Korvatska Olena, Piven Joseph, Sonnenblick Lisa I, Alvarez Retuerto Ana I, Herman Edward I, Dong Hongmei, Hutman Ted, Sigman Marian, Ozonoff Sally, Klin Ami, Owley Thomas, Sweeney John A, Brune Camille W, Cantor Rita M, Bernier Raphael, Gilbert John R, Cuccaro Michael L, McMahon William M, Miller Judith, State Matthew W, Wassink Thomas H, Coon Hilary, Levy Susan E, Schultz Robert T, Nurnberger John I, Haines Jonathan L, Sutcliffe James S, Cook Edwin H, Minshew Nancy J, Buxbaum Joseph D, Dawson Geraldine, Grant Struan F A, Geschwind Daniel H, Pericak-Vance Margaret A, Schellenberg Gerard D, Hakonarson Hakon in Nature (2009). PubMed

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.

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