Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Mol Psychiatry. 2018 May;23(5):1205-1212. doi: 10.1038/mp.2017.98. Epub 2017 May 16.
Autism spectrum disorders (ASDs) and autistic traits in the general population may share genetic susceptibility factors. In this study, we investigated such potential overlap based on common genetic variants. We developed and validated a self-report questionnaire of autistic traits in adults. We then conducted genome-wide association studies (GWASs) of six trait scores derived from the questionnaire through exploratory factor analysis in 1981 adults from the general population. Using the results from the Psychiatric Genomics Consortium GWAS of ASDs, we observed genetic sharing between ASDs and the autistic traits 'childhood behavior', 'rigidity' and 'attention to detail'. Gene-set analysis subsequently identified 'rigidity' to be significantly associated with a network of ASD gene-encoded proteins that regulates neurite outgrowth. Gene-wide association with the well-established ASD gene MET reached significance. Taken together, our findings provide evidence for an overlapping genetic and biological etiology underlying ASDs and autistic population traits, which suggests that genetic studies in the general population may yield novel ASD genes.
自闭症谱系障碍（ASD）和一般人群中的自闭症特征可能具有共同的遗传易感因素。在这项研究中，我们基于常见的遗传变异来研究这种潜在的重叠。我们开发并验证了一种成人自闭症特征的自我报告问卷。然后，我们通过对来自普通人群的 1981 名成年人进行探索性因素分析，对从问卷中得出的六个特征评分进行全基因组关联研究（GWAS）。利用精神疾病基因组学联盟 ASD 的 GWAS 结果，我们观察到 ASD 和自闭症特征“儿童行为”、“刻板性”和“注重细节”之间存在遗传共享。随后的基因集分析表明，“刻板性”与调节神经突生长的一组 ASD 基因编码蛋白的网络显著相关。与公认的 ASD 基因 MET 的全基因关联达到显著水平。总之，我们的研究结果为 ASD 和自闭症人群特征的遗传和生物学病因提供了证据，这表明一般人群中的遗传研究可能会产生新的 ASD 基因。
