Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
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DOI：
10.1038/s41467-019-10461-0
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发表时间：
2019-06-11
影响因子：
16.6
通讯作者：
Sullivan, Patrick F.
中科院分区：
文献类型：
--
作者：
Czamara, Darina;Eraslan, Goekcen;Sullivan, Patrick F.
表观遗传过程，包括DNA甲基化(DNaM)，是允许遗传和环境因素整合以塑造细胞功能的机制之一。虽然许多研究调查了环境或遗传因素对dNaM的影响，但很少有人评估它们的综合影响。在这里，我们在4个独立的队列中检验了产前环境因素和基因对新生儿血液中可变甲基化区域(VMR)DNA甲基化的相对贡献(总体n=2365)。我们使用Akaike的信息标准来检验哪些因素最好地解释了队列特异性VMR中甲基化的变异性：几个产前环境因素(E)、顺式(G)中的基因型、或它们的相加(G+E)或交互作用(GxE)效应。遗传因素和环境因素的共同作用最好地解释了大多数VMRS的dNaM。G、G+E或GxE最好解释的CPG在功能上是不同的。GWAGxE模型中针对复杂疾病的遗传变异的丰富支持了它们对疾病风险的重要性。
Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.