Independent and joint effects of the MAPT and SNCA genes in Parkinson disease.
Independent and joint effects of the MAPT and SNCA genes in Parkinson disease.
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DOI：
10.1002/ana.22321
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发表时间：
2011-05
影响因子：
11.2
通讯作者：
Farrer, Matthew J.
中科院分区：
文献类型：
--
作者：
Elbaz, Alexis;Ross, Owen A.;Ioannidis, John P. A.;Soto-Ortolaza, Alexandra I.;Moisan, Frederic;Aasly, Jan;Annesi, Grazia;Bozi, Maria;Brighina, Laura;Chartier-Harlin, Marie-Christine;Destee, Alain;Ferrarese, Carlo;Ferraris, Alessandro;Gibson, J. Mark;Gispert, Suzana;Hadjigeorgiou, Georgios M.;Jasinska-Myga, Barbara;Klein, Christine;Krueger, Rejko;Lambert, Jean-Charles;Lohmann, Katja;van de Loo, Simone;Loriot, Marie-Anne;Lynch, Timothy;Mellick, George D.;Mutez, Eugenie;Nilsson, Christer;Opala, Grzegorz;Puschmann, Andreas;Quattrone, Aldo;Sharma, Manu;Silburn, Peter A.;Stefanis, Leonidas;Uitti, Ryan J.;Valente, Enza Maria;Vilarino-Gueell, Carles;Wirdefeldt, Karin;Wszolek, Zbigniew K.;Xiromerisiou, Georgia;Maraganore, Demetrius M.;Farrer, Matthew J.
我们研究了编码α-突触核蛋白（SNCA）和微管相关蛋白tau（MAPT）的基因在帕金森病（PD）中的独立和联合作用，作为参与帕金森病遗传流行病学（GEO-PD）联盟的病例对照研究个体数据的大型荟萃分析的一部分。对高加索血统的参与者进行了总共四种SNCA（rs 2583988，rs 181489，rs356219，rs 11931074）和两种MAPT（rs 1052553，rs 242557）SNP的基因分型。SNCA和MAPT SNP的个体和联合效应使用固定和随机效应logistic回归模型进行了研究。相互作用进行了研究的乘法和加法规模，并使用病例对照和病例的方法。15个GEO-PD研究中心共提供了5302例病例和4161例对照。所有四个SNCA SNP和MAPT H1单倍型定义SNP（rs 1052553）在多重比较调整的显著性水平上显示出与PD高度显著的边缘相关性。对于SNCA，位于基因3′端的SNP观察到最强的关联。四个SNCA SNP中的任何一个与rs 1052553或rs 242557之间没有统计学相互作用的证据，无论是在乘法还是在加法尺度上。本研究证实了PD与SNCA SNP和H1 MAPT单倍型之间的关联。它表明，基于各种方法，在这两个基因座中的变体的联合作用与基因的独立效应一致，而没有额外的相互作用效应。
We studied the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule associated protein tau (MAPT) in Parkinson's disease (PD) as part of a large meta-analysis of individual data from case-control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) consortium. Participants of Caucasian ancestry were genotyped for a total of four SNCA (rs2583988, rs181489, rs356219, rs11931074) and two MAPT (rs1052553, rs242557) SNPs. Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed- and random-effects logistic regression models. Interactions were studied both on a multiplicative and an additive scale, and using a case-control and case-only approach. Fifteen GEO-PD sites contributed a total of 5302 cases and 4161 controls. All four SNCA SNPs and the MAPT H1-haplotype defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 3′ end of the gene. There was no evidence of statistical interaction between any of the four SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these two loci is consistent with independent effects of the genes without additional interacting effects.
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DOI：
10.1038/nrg2579
发表时间：
2009-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Cordell HJ
通讯作者：
Cordell HJ
影响因子：
11.2
作者：
Goris, An;Williams-Gray, Caroline H.;Sawcer, Stephen J.
通讯作者：
Sawcer, Stephen J.
影响因子：
3.5
作者：
Baker, M;Litvan, I;Hutton, M
通讯作者：
Hutton, M
影响因子：
5
作者：
ROTHMAN, KJ;GREENLAND, S;WALKER, AM
通讯作者：
WALKER, AM
影响因子：
9.8
作者：
Cordell, HJ;Clayton, DG
通讯作者：
Clayton, DG