Phenotypic effects of genetic variants associated with autism.
Phenotypic effects of genetic variants associated with autism.
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DOI：
10.1038/s41591-023-02408-2
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发表时间：
2023-07
期刊：
影响因子：
82.9
通讯作者：
Bourgeron, Thomas
中科院分区：
文献类型：
--
作者：
Rolland, Thomas;Cliquet, Freddy;Anney, Richard J. L.;Moreau, Clara;Traut, Nicolas;Mathieu, Alexandre;Huguet, Guillaume;Duan, Jinjie;Warrier, Varun;Portalier, Swan;Dry, Louise;Leblond, Claire S.;Douard, Elise;Amsellem, Frederique;Malesys, Simon;Maruani, Anna;Toro, Roberto;Borglum, Anders D.;Grove, Jakob;Baron-Cohen, Simon;Packer, Alan;Chung, Wendy K.;Jacquemont, Sebastien;Delorme, Richard;Bourgeron, Thomas
虽然有超过100个基因与自闭症有关，但人们对没有自闭症诊断的个体中影响它们的变异的流行率知之甚少。我们也没有充分认识到正式自闭症诊断之外的表型多样性。基于来自13，000多名自闭症患者和210，000名未确诊个体的数据，我们估计了与自闭症相关的185个基因中罕见功能丧失（LoF）变异相关的自闭症的比值比，以及2，492个对LoF变异表现出不耐受的基因。与以自闭症为中心的方法相反，我们研究了没有诊断出自闭症的个体中这些变异的相关性。我们发现，这些变异与流体智力、资格水平和收入的小幅但显著的下降以及与物质匮乏相关的指标的增加有关。自闭症相关基因的这些影响大于其他LoF不耐受基因。使用来自英国生物银行的21，040名个体的脑成像数据，我们无法检测到LoF携带者和非携带者之间的整体脑解剖结构的显着差异。我们的研究结果强调了研究分类诊断之外的遗传变异影响的重要性，以及需要更多的研究来了解这些变异与社会人口因素之间的关联，以最好地支持携带这些变异的个体。对来自20多万人的数据进行分析，确定了与自闭症相关基因中携带变异相关的表型特征，无论是否诊断为自闭症。
While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, we estimated the odds ratios for autism associated to rare loss-of-function (LoF) variants in 185 genes associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the correlates of these variants in individuals without a diagnosis of autism. We show that these variants are associated with a small but significant decrease in fluid intelligence, qualification level and income and an increase in metrics related to material deprivation. These effects were larger for autism-associated genes than in other LoF-intolerant genes. Using brain imaging data from 21,040 individuals from the UK Biobank, we could not detect significant differences in the overall brain anatomy between LoF carriers and non-carriers. Our results highlight the importance of studying the effect of the genetic variants beyond categorical diagnosis and the need for more research to understand the association between these variants and sociodemographic factors, to best support individuals carrying these variants. Analyses of data from more than 200,000 individuals identify phenotypic features associated to carrying variants in autism-associated genes, in individuals with and without a diagnosis of autism.
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错义突变热点识别神经发育障碍基因和功能域
影响因子：
25
作者：
Geisheker MR;Heymann G;Wang T;Coe BP;Turner TN;Stessman HAF;Hoekzema K;Kvarnung M;Shaw M;Friend K;Liebelt J;Barnett C;Thompson EM;Haan E;Guo H;Anderlid BM;Nordgren A;Lindstrand A;Vandeweyer G;Alberti A;Avola E;Vinci M;Giusto S;Pramparo T;Pierce K;Nalabolu S;Michaelson JJ;Sedlacek Z;Santen GWE;Peeters H;Hakonarson H;Courchesne E;Romano C;Kooy RF;Bernier RA;Nordenskjöld M;Gecz J;Xia K;Zweifel LS;Eichler EE
通讯作者：
Eichler EE
影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
DOI：
10.1176/appi.ajp.2020.20010015
发表时间：
2021-01-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Chawner SJRA;Doherty JL;Anney RJL;Antshel KM;Bearden CE;Bernier R;Chung WK;Clements CC;Curran SR;Cuturilo G;Fiksinski AM;Gallagher L;Goin-Kochel RP;Gur RE;Hanson E;Jacquemont S;Kates WR;Kushan L;Maillard AM;McDonald-McGinn DM;Mihaljevic M;Miller JS;Moss H;Pejovic-Milovancevic M;Schultz RT;Green-Snyder L;Vorstman JA;Wenger TL;IMAGINE-ID Consortium;Hall J;Owen MJ;van den Bree MBM
通讯作者：
van den Bree MBM
DOI：
10.1056/nejmsr1809937
发表时间：
2019-08-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
All of Us Research Program Investigators;Denny JC;Rutter JL;Goldstein DB;Philippakis A;Smoller JW;Jenkins G;Dishman E
通讯作者：
Dishman E
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian