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

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

Nature (2009-05-01)

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

PMID19404256

초록

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.