Abstract：
Multivariate network-based analytic methods such as weighted gene co-expression network analysis are frequently applied to human and animal gene-expression data to estimate the first principal component of a module, or module eigengene (ME). MEs are interpreted as multivariate summaries of correlated gene-expression patterns and network connectivity across genes within a module. As such, they have the potential to elucidate the mechanisms by which molecular genomic variation contributes to individual differences in complex traits. Although increasingly used to test for associations between modules and complex traits, the genetic and environmental etiology of MEs has not been empirically established. It is unclear if, and to what degree, individual differences in blood-derived MEs reflect random variation versus familial aggregation arising from heritable or shared environmental influences. We used biometrical genetic analyses to estimate the contribution of genetic and environmental influences on MEs derived from blood lymphocytes collected on a sample of N = 661 older male twins from the Vietnam Era Twin Study of Aging (VETSA) whose mean age at assessment was 67.7 years (SD = 2.6 years, range = 62-74 years). Of the 26 detected MEs, 14 (56%) had statistically significant additive genetic variation with an average heritability of 44% (SD = 0.08, range = 35%-64%). Despite the relatively small sample size, this demonstration of significant family aggregation including estimates of heritability in 14 of the 26 MEs suggests that blood-based MEs are reliable and merit further exploration in terms of their associations with complex traits and diseases.
摘要：
基于多变量网络的分析方法，如加权基因共表达网络分析经常应用于人类和动物基因表达数据，以估计模块的第一主成分。或模块特征基因(ME)。MEs被解释为模块内基因之间的相关基因表达模式和网络连接的多变量摘要。因此，它们有可能阐明分子基因组变异导致复杂性状个体差异的机制。尽管越来越多地用于测试模块和复杂特征之间的关联，尚未根据经验确定MEs的遗传和环境病因。目前还不清楚,到什么程度，血液来源MEs的个体差异反映了随机变异与遗传或共同环境影响引起的家族聚集。我们使用生物统计学遗传分析来估计遗传和环境影响对MEs的贡献，这些MEs来自越南时代双胞胎衰老研究（VETSA）的N=661对年龄较大的男性双胞胎的样本，其平均年龄为67.7岁（SD=2.6年，范围=62-74年)。在检测到的26个ME中，14（56％）具有统计学上显着的加性遗传变异，平均遗传力为44％（SD=0.08，范围=35％-64％）。尽管样本量相对较小，这一显著家庭聚集的证明,包括对26个MEs中的14个MEs的遗传力的估计,表明基于血液的MEs是可靠的,在它们与复杂性状和疾病的关联方面值得进一步探索.
