Joint testing of genotypic and gene-environment interaction identified novel association for BMP4 with non-syndromic CL/P in an Asian population using data from an International Cleft Consortium.
Joint testing of genotypic and gene-environment interaction identified novel association for BMP4 with non-syndromic CL/P in an Asian population using data from an International Cleft Consortium.
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基因型和基因环境相互作用的联合测试使用来自国际裂口财团的数据确定了亚洲人群中BMP4与非综合cl/p的新型关联。
DOI：
10.1371/journal.pone.0109038
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Beaty TH
中科院分区：
文献类型：
--
作者：
Chen Q;Wang H;Schwender H;Zhang T;Hetmanski JB;Chou YH;Ye X;Yeow V;Chong SS;Zhang B;Jabs EW;Parker MM;Scott AF;Beaty TH
非综合征性唇腭裂是一种病因复杂的常见疾病。骨形态发生蛋白4基因（Bone Morphogenetic Protein 4，BMP 4）是一个重要的候选基因，动物实验研究、人类连锁研究以及候选基因关联研究都提供了大量证据。本研究的目的是测试BMP 4和NSCL/P之间的连锁和关联，当仅考虑基因型（G）主效应时，全基因组关联研究（GWAS）可能会遗漏这些连锁和关联。我们在895名亚洲人和681名欧洲人完成的NSCL/P三人组中使用加性条件Logistic回归模型进行了考虑G和与多个母体环境暴露的相互作用的分析。在122个基因分型和25个基因内和基因周围的插补单核苷酸变异中通过质量控制标准的单核苷酸多态性（SNP）被用于分析。在怀孕前3个月和怀孕前三个月期间，选定的母体环境暴露包括任何个人吸烟，家中、工作场所或附近任何地方的任何环境吸烟，任何饮酒和任何使用多种维生素补充剂。Bonferroni矫正后，亚洲非先天性唇裂/先天性唇裂（NSCLP）三重奏与rs7156227之间存在一种新的显着相关性，当在等位基因或基因型传递不平衡测试中单独考虑G主效应时，并未观察到这种相关性。对于亚洲人NSCL/P和NSCLP三人组，携带一个拷贝的次要等位基因而母亲没有暴露于四种环境暴露中的任何一种的优势比分别为0.58（95%CI =0.44，0.75）和0.54（95%CI=0.40，0.73）。 相应地，针对117个测试SNP的总数校正的Bonferroni P值为0.0051（渐近P = 4.39*10 - 5）和0.0065（渐近P =5.54*10 - 5）。 在欧洲三人组中，在对总共120个测试的SNP进行Bonferroni校正后，没有发现任何SNP的显著相关性。我们的研究结果增加了来自GWAS的证据，以支持最初在连锁和候选基因关联研究中确定的BMP 4在NSCL/P易感性中的作用。
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered. We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10−5) and 0.0065 (asymptotic P = 5.54*10−5), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs. Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies.
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影响因子：
5.3
作者：
Beaty, T. H.;Taub, M. A.;Scott, A. F.;Murray, J. C.;Marazita, M. L.;Schwender, H.;Parker, M. M.;Hetmanski, J. B.;Balakrishnan, P.;Mansilla, M. A.;Mangold, E.;Ludwig, K. U.;Noethen, M. M.;Rubini, M.;Elcioglu, N.;Ruczinski, I.
通讯作者：
Ruczinski, I.
DOI：
10.1597/12-048
发表时间：
2013-11-01
期刊：
CLEFT PALATE-CRANIOFACIAL JOURNAL
影响因子：
--
作者：
Antunes, Leonardo Santos;Kuechler, Erika Calvano;Granjeiro, Jose Mauro
通讯作者：
Granjeiro, Jose Mauro
影响因子：
3.7
作者：
Jugessur A;Shi M;Gjessing HK;Lie RT;Wilcox AJ;Weinberg CR;Christensen K;Boyles AL;Daack-Hirsch S;Trung TN;Bille C;Lidral AC;Murray JC
通讯作者：
Murray JC
影响因子：
30.8
作者：
Birnbaum, Stefanie;Ludwig, Kerstin U.;Mangold, Elisabeth
通讯作者：
Mangold, Elisabeth
影响因子：
1.8
作者：
Marazita ML;Lidral AC;Murray JC;Field LL;Maher BS;Goldstein McHenry T;Cooper ME;Govil M;Daack-Hirsch S;Riley B;Jugessur A;Felix T;Morene L;Mansilla MA;Vieira AR;Doheny K;Pugh E;Valencia-Ramirez C;Arcos-Burgos M
通讯作者：
Arcos-Burgos M