Rare variants and the oligogenic architecture of autism.
Rare variants and the oligogenic architecture of autism.
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DOI：
10.1016/j.tig.2022.03.009
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发表时间：
2022-09
影响因子：
11.4
通讯作者：
Eichler, Evan E.
中科院分区：
文献类型：
--
作者：
Wang, Tianyun;Zhao, Peiyao A.;Eichler, Evan E.
大多数自闭症的大规模遗传学研究都集中在通过证明自闭症先证者中新生突变的富集或基于常见变异的关联来表征多基因风险来发现基因。我们目前的证据支持寡基因模型，其中两个或更多的超罕见突变更温和的影响，优先传输到自闭症儿童。这种私人基因破坏性突变在有多个受影响个体的家庭中富集，出现在2-3代人之前，并映射到以前与自闭症无关的基因。虽然没有一个单一的基因达到统计学意义，这类变异应考虑沿着遗传和非遗传因素，以更好地解释这种复杂性状的病因。
Most large-scale genetic studies of autism have focused on the discovery of genes by proving an enrichment of de novo mutations in autism probands or characterizing polygenic risk based on the association of common variants. We present evidence in support of an oligogenic model where two or more ultra-rare mutations of more modest effect are preferentially transmitted to children with autism. Such private gene-disruptive mutations are enriched in families where there are multiple affected individuals, emerged 2–3 generations ago, and map to genes not previously associated with autism. Although no single gene has reached statistical significance, this class of variation should be considered along with genetic and non-genetic factors to better explain the etiology of this complex trait.
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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
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
血液DNA甲基化和自闭症谱系障碍的病例对照荟萃分析。
影响因子：
6.2
作者：
Andrews SV;Sheppard B;Windham GC;Schieve LA;Schendel DE;Croen LA;Chopra P;Alisch RS;Newschaffer CJ;Warren ST;Feinberg AP;Fallin MD;Ladd-Acosta C
通讯作者：
Ladd-Acosta C
影响因子：
6.8
作者：
Homs A;Codina-Solà M;Rodríguez-Santiago B;Villanueva CM;Monk D;Cuscó I;Pérez-Jurado LA
通讯作者：
Pérez-Jurado LA
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