Genome-wide prediction and functional characterization of the genetic basis of autism spectrum disorder.
Genome-wide prediction and functional characterization of the genetic basis of autism spectrum disorder.
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DOI：
10.1038/nn.4353
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发表时间：
2016-11
影响因子：
25
通讯作者：
Troyanskaya OG
中科院分区：
文献类型：
--
作者：
Krishnan A;Zhang R;Yao V;Theesfeld CL;Wong AK;Tadych A;Volfovsky N;Packer A;Lash A;Troyanskaya OG
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，具有很强的遗传基础。然而，只有一小部分潜在的致病基因——大约数百个基因中的大约 65 个——是通过测序研究获得强有力的遗传证据的。我们开发了一种基于人脑特定基因网络的补充机器学习方法，以提出自闭症风险基因的全基因组预测，其中包括数百个先前遗传证据很少或没有的候选基因。我们的方法在一项大型独立病例对照测序研究中得到了验证。利用这些全基因组预测和大脑特定网络，我们证明大量自闭症谱系障碍基因集中在大脑的较少数量的关键通路和发育阶段。最后，我们鉴定了常见的自闭症相关拷贝数变异中可能的致病基因，并提出了可能是多个拷贝数变异中自闭症谱系障碍介导因素的基因和途径。所有预测和功能见解均可在 http://asd.princeton.edu 上获取。
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic basis. Yet, only a small fraction of potentially causal genes—about 65 genes out of an estimated several hundred—are known with strong genetic evidence from sequencing studies. We developed a complementary machine-learning approach based on a human brain-specific gene network to present a genome-wide prediction of autism risk genes, including hundreds of candidates for which there is minimal or no prior genetic evidence. Our approach was validated in a large independent case–control sequencing study. Leveraging these genomewide predictions and the brain-specific network, we demonstrated that the large set of ASD genes converges on a smaller number of key pathways and developmental stages of the brain. Finally, we identified likely pathogenic genes within frequent autism-associated copy-number variants and proposed genes and pathways that are likely mediators of ASD across multiple copy-number variants. All predictions and functional insights are available at http://asd.princeton.edu.
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影响因子：
16.2
作者：
Iossifov I;Ronemus M;Levy D;Wang Z;Hakker I;Rosenbaum J;Yamrom B;Lee YH;Narzisi G;Leotta A;Kendall J;Grabowska E;Ma B;Marks S;Rodgers L;Stepansky A;Troge J;Andrews P;Bekritsky M;Pradhan K;Ghiban E;Kramer M;Parla J;Demeter R;Fulton LL;Fulton RS;Magrini VJ;Ye K;Darnell JC;Darnell RB;Mardis ER;Wilson RK;Schatz MC;McCombie WR;Wigler M
通讯作者：
Wigler M
影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
11
作者：
Di Martino, A.;Yan, C-G;Li, Q.;Denio, E.;Castellanos, F. X.;Alaerts, K.;Anderson, J. S.;Assaf, M.;Bookheimer, S. Y.;Dapretto, M.;Deen, B.;Delmonte, S.;Dinstein, I.;Ertl-Wagner, B.;Fair, D. A.;Gallagher, L.;Kennedy, D. P.;Keown, C. L.;Keysers, C.;Lainhart, J. E.;Lord, C.;Luna, B.;Menon, V.;Minshew, N. J.;Monk, C. S.;Mueller, S.;Mueller, R. A.;Nebel, M. B.;Nigg, J. T.;O'Hearn, K.;Pelphrey, K. A.;Peltier, S. J.;Rudie, J. D.;Sunaert, S.;Thioux, M.;Tyszka, J. M.;Uddin, L. Q.;Verhoeven, J. S.;Wenderoth, N.;Wiggins, J. L.;Mostofsky, S. H.;Milham, M. P.
通讯作者：
Milham, M. P.
影响因子：
7
作者：
Hormozdiari F;Penn O;Borenstein E;Eichler EE
通讯作者：
Eichler EE
自闭症相关的染色质修饰剂CHD8在人神经发育过程中调节其他自闭症风险基因。
影响因子：
16.6
作者：
Cotney, Justin;Muhle, Rebecca A.;Sanders, Stephan J.;Liu, Li;Willsey, A. Jeremy;Niu, Wei;Liu, Wenzhong;Klei, Lambertus;Lei, Jing;Yin, Jun;Reilly, Steven K.;Tebbenkamp, Andrew T.;Bichsel, Candace;Pletikos, Mihovil;Sestan, Nenad;Roeder, Kathryn;State, Matthew W.;Devlin, Bernie;Noonan, James P.
通讯作者：
Noonan, James P.