Identification of common genetic risk variants for autism spectrum disorder
Identification of common genetic risk variants for autism spectrum disorder
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DOI：
10.1038/s41588-019-0344-8
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发表时间：
2019-03-01
期刊：
影响因子：
30.8
通讯作者：
Wilson, Catherine H.
中科院分区：
文献类型：
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作者：
Grove, Jakob;Ripke, Stephan;Wilson, Catherine H.
自闭症谱系障碍 (ASD) 是一组具有高度遗传性和异质性的神经发育表型，在超过 1% 的儿童中被诊断出来。常见的遗传变异对自闭症谱系障碍（ASD）易感性有很大影响，但迄今为止，还没有任何个体变异与自闭症谱系障碍（ASD）密切相关。随着丹麦独特人口资源的样本量显着增加，我们报告了对 18,381 名自闭症谱系障碍患者和 27,969 名对照者进行的全基因组关联荟萃分析，确定了 5 个全基因组显着位点。利用遗传结构显着重叠的三种表型（精神分裂症、重度抑郁症和教育程度）的 GWAS 结果，我们确定了与其他性状在同样严格的显着性水平上共享的另外七个位点。通过剖析多基因结构，我们发现 ASD 亚型之间存在定量和定性的多基因异质性。这些结果突出了生物学见解，特别是与神经元功能和皮质生成相关的生物学见解，并证实大规模进行的 GWAS 在近期内将在自闭症谱系障碍中更加有效。
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.