Fernández-Rhodes Lindsay, Howard Annie Green, Tao Ran, Young Kristin L, Graff Mariaelisa, Aiello Allison E, North Kari E, Justice Anne E
Department of Epidemiology, University of North Carolina at Chapel Hill, 137 East Franklin Street, Chapel Hill, NC, 27514, USA.
Carolina Population Center, University of North Carolina at Chapel Hill, 136 East Franklin Street, Chapel Hill, NC, 27514, USA.
BMC Genet. 2018 Sep 17;19(Suppl 1):69. doi: 10.1186/s12863-018-0634-7.
Transgenerational epigenetic inheritance has been posited as a possible contributor to the observed heritability of metabolic syndrome (MetS). Yet the extent to which estimates of epigenetic inheritance for DNA methylation sites are inflated by environmental and genetic covariance within families is still unclear. We applied current methods to quantify the environmental and genetic contributors to the observed heritability and familial correlations of four previously associated MetS methylation sites at three genes (CPT1A, SOCS3 and ABCG1) using real data made available through the GAW20.
Our findings support the role of both shared environment and genetic variation in explaining the heritability of MetS and the four MetS cytosine-phosphate-guanine (CpG) sites, although the resulting heritability estimates were indistinguishable from one another. Familial correlations by type of relative pair generally followed our expectation based on relatedness, but in the case of sister and parent pairs we observed nonsignificant trends toward greater correlation than expected, as would be consistent with the role of shared environmental factors in the inflation of our estimated correlations.
Our work provides an interesting and flexible statistical framework for testing models of epigenetic inheritance in the context of human family studies. Future work should endeavor to replicate our findings and advance these methods to more robustly describe epigenetic inheritance patterns in human populations.
跨代表观遗传继承被认为可能是导致观察到的代谢综合征（MetS）遗传力的一个因素。然而，家庭内部环境和遗传协方差对DNA甲基化位点表观遗传继承估计值的夸大程度仍不清楚。我们应用当前方法，利用GAW20提供的真实数据，量化环境和遗传因素对三个基因（CPT1A、SOCS3和ABCG1）中四个先前关联的MetS甲基化位点的观察到的遗传力和家族相关性的贡献。
我们的研究结果支持共享环境和遗传变异在解释MetS遗传力以及四个MetS胞嘧啶-磷酸-鸟嘌呤（CpG）位点方面的作用，尽管由此产生的遗传力估计值彼此无法区分。按亲属对类型划分的家族相关性总体上符合我们基于亲缘关系的预期，但在姐妹对和父母对的情况下，我们观察到相关性高于预期的不显著趋势，这与共享环境因素在夸大我们估计的相关性方面的作用一致。
我们的工作为在人类家庭研究背景下测试表观遗传继承模型提供了一个有趣且灵活的统计框架。未来的工作应努力重复我们的研究结果，并改进这些方法，以更有力地描述人类群体中的表观遗传继承模式。
