https://scholars.lib.ntu.edu.tw/handle/123456789/585389
標題: | Exome sequencing in schizophrenia-affected parent–offspring trios reveals risk conferred by protein-coding de novo mutations | 作者: | Howrigan D.P. Rose S.A. Samocha K.E. Fromer M. Cerrato F. WEI J. CHEN Churchhouse C. Chambert K. Chandler S.D. Daly M.J. Dumont A. Genovese G. HAI-GWO HWU Laird N. Kosmicki J.A. Moran J.L. Roe C. Singh T. Wang S.-H. Faraone S.V. Glatt S.J. McCarroll S.A. Tsuang M. Neale B.M. |
公開日期: | 2020 | 卷: | 23 | 期: | 2 | 起(迄)頁: | 185-193 | 來源出版物: | Nature Neuroscience | 摘要: | Protein-coding de novo mutations (DNMs) are significant risk factors in many neurodevelopmental disorders, whereas schizophrenia (SCZ) risk associated with DNMs has thus far been shown to be modest. We analyzed DNMs from 1,695 SCZ-affected trios and 1,077 published SCZ-affected trios to better understand the contribution to SCZ risk. Among 2,772 SCZ probands, exome-wide DNM burden remained modest. Gene set analyses revealed that SCZ DNMs were significantly concentrated in genes that were highly expressed in the brain, that were under strong evolutionary constraint and/or overlapped with genes identified in other neurodevelopmental disorders. No single gene surpassed exome-wide significance; however, 16 genes were recurrently hit by protein-truncating DNMs, corresponding to a 3.15-fold higher rate than the mutation model expectation (permuted 95% confidence interval: 1–10 genes; permuted P = 3 × 10? 5). Overall, DNMs explain a small fraction of SCZ risk, and larger samples are needed to identify individual risk genes, as coding variation across many genes confers risk for SCZ in the population. ? 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85078625629&doi=10.1038%2fs41593-019-0564-3&partnerID=40&md5=9dc5f26bec51ad4f80e3af19d4d8e996 https://scholars.lib.ntu.edu.tw/handle/123456789/585389 |
ISSN: | 10976256 | DOI: | 10.1038/s41593-019-0564-3 | SDG/關鍵字: | adult; Article; autism; controlled study; developmental delay; DNA barcoding; female; gene expression; gene mutation; genetic association; genetic variation; human; intellectual impairment; major clinical study; male; parent; priority journal; progeny; protein coding de novo mutation; risk assessment; schizophrenia; synapse; Taiwan; Taiwanese; whole exome sequencing; child; child parent relation; family; genetic predisposition; genetics; mutation; schizophrenia; whole exome sequencing; Adult; Child; Family; Female; Genetic Predisposition to Disease; Humans; Male; Mutation; Parents; Schizophrenia; Whole Exome Sequencing |
顯示於: | 醫學院附設醫院 (臺大醫院) |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。