Defining the contribution of CNTNAP2 to autism susceptibility.
Defining the contribution of CNTNAP2 to autism susceptibility.
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DOI：
10.1371/journal.pone.0077906
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chakravarti A
中科院分区：
文献类型：
--
作者：
Sampath S;Bhat S;Gupta S;O'Connor A;West AB;Arking DE;Chakravarti A
多条遗传证据表明CNTNAP 2在自闭症中的作用。为了评估其对人群的影响，我们研究了2148个常见的单核苷酸多态性（SNPs），使用传递不平衡检验（TDT）在整个~3.3 Mb CNTNAP 2基因座在186（408个三重）和323个孤独症谱系障碍（ASD）的家庭。该分析产生了两个具有标称统计学显著性的SNP（rs 17170073，p = 2.0 x 10-4; rs 2215798，p = 1.6 x 10-4），其未经受多次测试。在对所有家族的综合分析中，内含子14中的两个高度相关（r2 = 0.99）的SNP显示与自闭症显著相关（rs 2710093，p = 9.0 x 10-6; rs 2253031，p = 2.5 x 10-5）。为了验证这些发现和先前自闭症研究（rs7794745，rs 2710102和rs 17236239）中SNP的相关性，我们对另外2051个家庭进行了基因分型（572个多重和1479个单纯）。在多次测试校正后，这些变异均与ASD无显著相关。在每个家庭内的孟德尔错误的分析没有显示任何分离缺失。然而，一项对自闭症患者和正常对照者大脑中CNTNAP 2基因表达的研究表明，一部分患者的表达发生了改变（p = 1.9 x10-5）。因此，这项研究表明，虽然CNTNAP 2失调在某些情况下发挥作用，但其对自闭症易感性的人口贡献有限。
Multiple lines of genetic evidence suggest a role for CNTNAP2 in autism. To assess its population impact we studied 2148 common single nucleotide polymorphisms (SNPs) using transmission disequilibrium test (TDT) across the entire ~3.3 Mb CNTNAP2 locus in 186 (408 trios) multiplex and 323 simplex families with autistic spectrum disorder (ASD). This analysis yielded two SNPs with nominal statistical significance (rs17170073, p = 2.0 x 10-4; rs2215798, p = 1.6 x 10-4) that did not survive multiple testing. In a combined analysis of all families, two highly correlated (r 2 = 0.99) SNPs in intron 14 showed significant association with autism (rs2710093, p = 9.0 x 10-6; rs2253031, p = 2.5 x 10-5). To validate these findings and associations at SNPs from previous autism studies (rs7794745, rs2710102 and rs17236239) we genotyped 2051 additional families (572 multiplex and 1479 simplex). None of these variants were significantly associated with ASD after corrections for multiple testing. The analysis of Mendelian errors within each family did not indicate any segregating deletions. Nevertheless, a study of CNTNAP2 gene expression in brains of autistic patients and of normal controls, demonstrated altered expression in a subset of patients (p = 1.9 x10-5). Consequently, this study suggests that although CNTNAP2 dysregulation plays a role in some cases, its population contribution to autism susceptibility is limited.
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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：
4
作者：
Bill, Brent R.;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.
影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
6.9
作者：
BAILEY, A;LECOUTEUR, A;RUTTER, M
通讯作者：
RUTTER, M
影响因子：
2.1
作者：
Blangero, J;Williams, JT;Almasy, L
通讯作者：
Almasy, L