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
Center for Applied Genomics, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Nature. 2009 May 28;459(7246):528-33. doi: 10.1038/nature07999. Epub 2009 Apr 28.
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.
自闭症谱系障碍（ASD）是一组儿童神经发育和神经精神障碍，其特征为言语交流缺陷、社交互动受损以及兴趣和行为模式受限且重复。为了确定ASD潜在的常见遗传风险因素，我们在此展示了针对780个有患病儿童的家庭（3101名受试者）以及另一组由1204名患病受试者和6491名对照受试者组成的队列进行的全基因组关联研究结果，所有这些受试者均为欧洲血统。钙黏蛋白10（CDH10）和钙黏蛋白9（CDH9）（两个编码神经元细胞黏附分子的基因）之间的六个单核苷酸多态性显示出强烈的关联信号，最显著的单核苷酸多态性为rs4307059（P = 3.4×10⁻⁸，优势比 = 1.19）。这些信号在两个独立队列中得到重复，合并后的P值范围为7.4×10⁻⁸至2.1×10⁻¹⁰。我们的结果表明神经元细胞黏附分子与ASD的发病机制有关，据我们所知，这是首次证明常见变异与ASD易感性存在全基因组显著关联。
