Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations.
Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations.
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DOI：
10.1038/s41467-021-25532-4
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发表时间：
2021-09-09
影响因子：
16.6
通讯作者：
O'Donovan MC
中科院分区：
文献类型：
--
作者：
Rees E;Creeth HDJ;Hwu HG;Chen WJ;Tsuang M;Glatt SJ;Rey R;Kirov G;Walters JTR;Holmans P;Owen MJ;O'Donovan MC
精神分裂症患者在与神经发育障碍相关的基因中富含罕见的编码变体，特别是自闭症谱系障碍和智力残疾。然而，目前尚不清楚增加神经发育障碍风险的基因功能变化是否也会导致精神分裂症。使用来自3444例精神分裂症三人组和37,488例神经发育障碍三人组的数据，我们表明，在共享的风险基因中，精神分裂症和神经发育障碍的新生变异通常具有相同的功能类别，并且在神经发育障碍中观察到的特异性新生变异在精神分裂症中富集（P = 5.0 × 10−6）。后者包括已知为综合征性疾病的致病性的变体，这表明精神分裂症被包括为这些综合征的特征。我们的研究结果意味着，在某种程度上，神经发育障碍和精神分裂症有共同的分子病因学，因此可能重叠的病理生理学，并支持这一假设，至少有一些形式的精神分裂症在于连续的神经发育障碍。重叠基因与精神分裂症和神经发育障碍有关。在这里，作者在两种类型的疾病中重叠了从头变异，并在这些基因中发现了具有相同功能效应的变异，在某些情况下是相同的特异性变异。
People with schizophrenia are enriched for rare coding variants in genes associated with neurodevelopmental disorders, particularly autism spectrum disorders and intellectual disability. However, it is unclear if the same changes to gene function that increase risk to neurodevelopmental disorders also do so for schizophrenia. Using data from 3444 schizophrenia trios and 37,488 neurodevelopmental disorder trios, we show that within shared risk genes, de novo variants in schizophrenia and neurodevelopmental disorders are generally of the same functional category, and that specific de novo variants observed in neurodevelopmental disorders are enriched in schizophrenia (P = 5.0 × 10−6). The latter includes variants known to be pathogenic for syndromic disorders, suggesting that schizophrenia be included as a characteristic of those syndromes. Our findings imply that, in part, neurodevelopmental disorders and schizophrenia have shared molecular aetiology, and therefore likely overlapping pathophysiology, and support the hypothesis that at least some forms of schizophrenia lie on a continuum of neurodevelopmental disorders. Overlapping genes have been implicated in schizophrenia and neurodevelopmental disorders. Here, the authors overlap de novo variants in the two types of disorders and find variants in these genes with the same functional effect and in some cases the same specific variants.
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影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
DOI：
10.1192/bjp.bp.110.084384
发表时间：
2011-03
期刊：
The British journal of psychiatry : the journal of mental science
影响因子：
--
作者：
Owen MJ;O'Donovan MC;Thapar A;Craddock N
通讯作者：
Craddock N
影响因子：
11
作者：
McCarthy, S. E.;Gillis, J.;Kramer, M.;Lihm, J.;Yoon, S.;Berstein, Y.;Mistry, M.;Pavlidis, P.;Solomon, R.;Ghiban, E.;Antoniou, E.;Kelleher, E.;O'Brien, C.;Donohoe, G.;Gill, M.;Morris, D. W.;McCombie, W. R.;Corvin, A.
通讯作者：
Corvin, A.
DOI：
10.1038/ejhg.2015.218
发表时间：
2016-06
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Ambalavanan A;Girard SL;Ahn K;Zhou S;Dionne-Laporte A;Spiegelman D;Bourassa CV;Gauthier J;Hamdan FF;Xiong L;Dion PA;Joober R;Rapoport J;Rouleau GA
通讯作者：
Rouleau GA
影响因子：
14.5
作者：
Mak, Christopher C. Y.;Doherty, Dan;Gordon, Christopher T.
通讯作者：
Gordon, Christopher T.