Rare coding variation provides insight into the genetic architecture and phenotypic context of autism

DOI HANDLE HANDLE HANDLE HANDLE ほか5件をすべて表示 一部だけ表示 研究データあり 被引用文献14件 参考文献2件 オープンアクセス

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公開日
2022-08-18
権利情報
  • https://www.springer.com/tdm
  • https://www.springer.com/tdm
DOI
  • 10.1038/s41588-022-01104-0
公開者
Springer Science and Business Media LLC

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説明

Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk. Meta-analysis with cohorts ascertained for developmental delay (DD) (n = 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk.

収録刊行物

  • Nature Genetics

    Nature Genetics 54 (9), 1320-1331, 2022-08-18

    Springer Science and Business Media LLC

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