Detecting maternal-fetal genotype interactions associated with conotruncal heart defects: a haplotype-based analysis with penalized logistic regression.
Detecting maternal-fetal genotype interactions associated with conotruncal heart defects: a haplotype-based analysis with penalized logistic regression.
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DOI：
10.1002/gepi.21793
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发表时间：
2014-04
影响因子：
2.1
通讯作者：
Cleves, Mario A.
中科院分区：
文献类型：
--
作者：
Li, Ming;Erickson, Stephen W.;Hobbs, Charlotte A.;Li, Jingyun;Tang, Xinyu;Nick, Todd G.;Macleod, Stewart L.;Cleves, Mario A.
关键词：
非综合征性先天性心脏病（CHD）是胚胎发育过程中环境暴露、遗传和表观遗传因素之间复杂相互作用的结果。与CHD相关的遗传因素可以归因于母体或胎儿基因的独立作用，或母体和胎儿基因之间的代际相互作用。检测复杂疾病背后的基因间相互作用是遗传学研究中的一个主要挑战。由于母体和胎儿基因组之间的相关性，检测母体-胎儿基因型（MFG）相互作用并将其与母体/胎儿主效应区分开来已经提出了额外的统计挑战。传统上，遗传变异分别测试母体/胎儿的主要影响和MFG的相互作用的单基因座的基础上。我们进行了一个单体型为基础的分析与惩罚逻辑回归框架，剖析与非综合征圆锥动脉干心脏缺陷（CTD）的发展相关的遗传效应。我们的方法允许同时进行模型选择和效应估计，提供了一个统一的框架，以区分母亲/胎儿的主要影响MFG的相互作用的影响。此外，该方法能够用单倍型配置同时测试多个高度连锁的SNP，这降低了数据维度和多重测试的负担。通过分析国家出生缺陷预防研究（NBDPS）的数据集，我们确定了与CTD发展相关的七个基因（GSTA 1，SOD 2，MTRR，AHCYL 2，GCLC，GSTM 3和RFC 1）。我们的研究结果表明，在7个基因，GCLC，GSTM 3和RFC 1，单倍型之间的MFG相互作用与非综合征圆锥动脉干心脏缺陷。
Non-syndromic congenital heart defects (CHDs) develop during embryogenesis as a result of a complex interplay between environmental exposures, genetics and epigenetic causes. Genetic factors associated with CHDs may be attributed to either independent effects of maternal or fetal genes, or the inter-generational interactions between maternal and fetal genes. Detecting gene-by-gene interactions underlying complex diseases is a major challenge in genetic research. Detecting maternal-fetal genotype (MFG) interactions and differentiating them from the maternal/fetal main effects has presented additional statistical challenges due to correlations between maternal and fetal genomes. Traditionally, genetic variants are tested separately for maternal/fetal main effects and MFG interactions on a single-locus basis. We conducted a haplotype-based analysis with a penalized logistic regression framework to dissect the genetic effect associated with the development of non-syndromic conotruncal heart defects (CTD). Our method allows simultaneous model selection and effect estimation, providing a unified framework to differentiate maternal/fetal main effect from the MFG interaction effect. In addition, the method is able to test multiple highly linked SNPs simultaneously with a configuration of haplotypes, which reduces the data dimensionality and the burden of multiple testing. By analyzing a dataset from the National Birth Defects Prevention Study (NBDPS), we identified seven genes (GSTA1, SOD2, MTRR, AHCYL2, GCLC, GSTM3 and RFC1) associated with the development of CTDs. Our findings suggest that MFG interactions between haplotypes in 3 of 7 genes, GCLC, GSTM3 and RFC1, are associated with non-syndromic conotruncal heart defects.
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DOI：
10.1002/bdra.20829
发表时间：
2011-07-01
影响因子：
--
作者：
Gallagher, Margaret L.;Sturchio, Cynthia;Rasmussen, Sonja A.
通讯作者：
Rasmussen, Sonja A.
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
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
1.8
作者：
Moore, JH
通讯作者：
Moore, JH
DOI：
10.1002/tera.10086
发表时间：
2002-10-01
期刊：
TERATOLOGY
影响因子：
--
作者：
Rasmussen, SA;Lammer, EJ;Murray, JC
通讯作者：
Murray, JC