几个方面的证据都表明，“泛自闭症障碍症候群”（ASDs）、神经发育和神经精神类疾病都与遗传有关，这些疾病的特征是语言沟通和社会互动能力受损。病症在临床和遗传上的复杂性使得研究人员难以识别易感因子，但本期Nature上发表的两项相关联的研究，为这类疾病与遗传有关提供了可靠证据。

第一项是整个基因组范围内的关联研究，识别出了6个与自闭症有很强相关性的单核苷酸多态性。这些变种分布在两个编码神经细胞粘附分子（cadherins 9 和10）的基因之间，说明它们可能在ASD发病机理中有所涉及。第二项研究利用版本数变化筛选方法来识别ASDs患儿两个主要基因通道中的基因变异。这些变异在泛素通道中，该通道以前被发现与神经类疾病有关；它们也在为神经细胞粘附分子编码的基因中。

推荐原始出处：

Nature 459, 528-533 (28 May 2009) | doi:10.1038/nature07999

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

Kai Wang1,22, Haitao Zhang1,22, Deqiong Ma2,22, Maja Bucan3, Joseph T. Glessner1, Brett S. Abrahams4, Daria Salyakina2, Marcin Imielinski1, Jonathan P. Bradfield1, Patrick M. A. Sleiman1, Cecilia E. Kim1, Cuiping Hou1, Edward Frackelton1, Rosetta Chiavacci1, Nagahide Takahashi5, Takeshi Sakurai5, Eric Rappaport6, Clara M. Lajonchere7, Jeffrey Munson8, Annette Estes8, Olena Korvatska8, Joseph Piven9, Lisa I. Sonnenblick4, Ana I. Alvarez Retuerto4, Edward I. Herman4, Hongmei Dong4, Ted Hutman4, Marian Sigman4, Sally Ozonoff10, Ami Klin11, Thomas Owley12, John A. Sweeney12, Camille W. Brune12, Rita M. Cantor13, Raphael Bernier8, John R. Gilbert2, Michael L. Cuccaro2, William M. McMahon14, Judith Miller14, Matthew W. State11, Thomas H. Wassink15, Hilary Coon14, Susan E. Levy6, Robert T. Schultz6, John I. Nurnberger16, Jonathan L. Haines17, James S. Sutcliffe18, Edwin H. Cook12, Nancy J. Minshew19, Joseph D. Buxbaum5,20, Geraldine Dawson8, Struan F. A. Grant1,6, Daniel H. Geschwind4, Margaret A. Pericak-Vance2, Gerard D. Schellenberg21 & Hakon Hakonarson1,6

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  10-8, odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4  10-8 to 2.1  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.