Individual common variants exert weak effects on the risk for autism spectrum disorders.
Individual common variants exert weak effects on the risk for autism spectrum disorders.
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DOI：
10.1093/hmg/dds301
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发表时间：
2012-11-01
影响因子：
3.5
通讯作者：
Devlin B
中科院分区：
文献类型：
--
作者：
Anney R;Klei L;Pinto D;Almeida J;Bacchelli E;Baird G;Bolshakova N;Bölte S;Bolton PF;Bourgeron T;Brennan S;Brian J;Casey J;Conroy J;Correia C;Corsello C;Crawford EL;de Jonge M;Delorme R;Duketis E;Duque F;Estes A;Farrar P;Fernandez BA;Folstein SE;Fombonne E;Gilbert J;Gillberg C;Glessner JT;Green A;Green J;Guter SJ;Heron EA;Holt R;Howe JL;Hughes G;Hus V;Igliozzi R;Jacob S;Kenny GP;Kim C;Kolevzon A;Kustanovich V;Lajonchere CM;Lamb JA;Law-Smith M;Leboyer M;Le Couteur A;Leventhal BL;Liu XQ;Lombard F;Lord C;Lotspeich L;Lund SC;Magalhaes TR;Mantoulan C;McDougle CJ;Melhem NM;Merikangas A;Minshew NJ;Mirza GK;Munson J;Noakes C;Nygren G;Papanikolaou K;Pagnamenta AT;Parrini B;Paton T;Pickles A;Posey DJ;Poustka F;Ragoussis J;Regan R;Roberts W;Roeder K;Roge B;Rutter ML;Schlitt S;Shah N;Sheffield VC;Soorya L;Sousa I;Stoppioni V;Sykes N;Tancredi R;Thompson AP;Thomson S;Tryfon A;Tsiantis J;Van Engeland H;Vincent JB;Volkmar F;Vorstman JA;Wallace S;Wing K;Wittemeyer K;Wood S;Zurawiecki D;Zwaigenbaum L;Bailey AJ;Battaglia A;Cantor RM;Coon H;Cuccaro ML;Dawson G;Ennis S;Freitag CM;Geschwind DH;Haines JL;Klauck SM;McMahon WM;Maestrini E;Miller J;Monaco AP;Nelson SF;Nurnberger JI Jr;Oliveira G;Parr JR;Pericak-Vance MA;Piven J;Schellenberg GD;Scherer SW;Vicente AM;Wassink TH;Wijsman EM;Betancur C;Buxbaum JD;Cook EH;Gallagher L;Gill M;Hallmayer J;Paterson AD;Sutcliffe JS;Szatmari P;Vieland VJ;Hakonarson H;Devlin B
虽然罕见变异在自闭症谱系障碍（ASD）的遗传结构中发挥重要作用是显而易见的，但常见变异对患ASD风险的贡献却不太清楚。为了产生更全面的画面，我们报告了自闭症基因组计划全基因组关联研究的第二阶段，增加了1301个ASD家庭，使分析的家庭总数达到2705个（第一阶段和第二阶段）。除了评估单个单核苷酸多态性（snp）的相关性外，我们还寻求证据表明，共同的变异可能会影响风险。尽管基因组中有超过一百万个SNP，但没有一个SNP在全基因组水平上显示出与ASD或选定表型的显著关联。二次分析p值最小的SNP是rs1718101。它位于CNTNAP2中，这是一种先前与ASD易感性有关的基因。该SNP也显示出与ASD受试者单词/短语习得年龄的适度关联，因为语言发展的特征也与CNTNAP2的其他变异有关。相比之下，在独立的第二阶段样本中，从普通等位基因传播到第一阶段病例中得出的等位基因得分可以显著预测病例状态。尽管具有显著性，但这些等位基因得分解释的方差很小（Vm< 1%）。根据单个snp的结果及其对风险的整体影响，从等位基因评分结果推断，可以合理地得出结论，常见变异会影响ASD的风险，但它们的个体影响是适度的。
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
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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：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
影响因子：
--
作者：
Gregor A;Albrecht B;Bader I;Bijlsma EK;Ekici AB;Engels H;Hackmann K;Horn D;Hoyer J;Klapecki J;Kohlhase J;Maystadt I;Nagl S;Prott E;Tinschert S;Ullmann R;Wohlleber E;Woods G;Reis A;Rauch A;Zweier C
通讯作者：
Zweier C
影响因子：
64.8
作者：
Cook, Edwin H., Jr.;Scherer, Stephen W.
通讯作者：
Scherer, Stephen W.
DOI：
10.1002/ajmg.b.31063
发表时间：
2010-06-05
影响因子：
2.8
作者：
Ching, Michael S. L.;Shen, Yiping;Tan, Wen-Hann;Jeste, Shafali S.;Morrow, Eric M.;Chen, Xiaoli;Mukaddes, Nahit M.;Yoo, Seung-Yun;Hanson, Ellen;Hundley, Rachel;Austin, Christina;Becker, Ronald E.;Berry, Gerard T.;Driscoll, Katherine;Engle, Elizabeth C.;Friedman, Sandra;Gusella, James F.;Hisama, Fuki M.;Irons, Mira B.;Lafiosca, Tina;LeClair, Elaine;Miller, David T.;Neessen, Michael;Picker, Jonathan D.;Rappaport, Leonard;Rooney, Cynthia M.;Sarco, Dean P.;Stoler, Joan M.;Walsh, Christopher A.;Wolff, Robert R.;Zhang, Ting;Nasir, Ramzi H.;Wu, Bai-Lin
通讯作者：
Wu, Bai-Lin