Sarnowski Chloé, Lent Samantha, Dupuis Josée
Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, MA, 02118, USA.
BMC Genet. 2018 Sep 17;19(Suppl 1):83. doi: 10.1186/s12863-018-0640-9.
Genome-wide association studies performed on triglycerides (TGs) have not accounted for epigenetic mechanisms that may partially explain trait heritability.
Parent-of-origin (POO) effect association analyses using an agnostic approach or a candidate approach were performed for pretreatment TG levels, posttreatment TG levels, and pre- and posttreatment TG-level differences in the real GAW20 family data set. We detected 22 genetic variants with suggestive POO effects with at least 1 phenotype (P ≤ 10). We evaluated the association of these 22 significant genetic variants showing POO effects with close DNA methylation probes associated with TGs. A total of 18 DNA methylation probes located in the vicinity of the 22 SNPs were associated with at least 1 phenotype and 6 SNP-probe pairs were associated with DNA methylation probes at the nominal level of P < 0.05, among which 1 pair presented evidence of POO effect. Our analyses identified a paternal effect of SNP rs301621 on the difference between pre- and posttreatment TG levels (P = 1.2 × 10). This same SNP showed evidence for a maternal effect on methylation levels of a nearby probe (cg10206250; P = 0.01). Using a causal inference test we established that the observed POO effect of rs301621 was not mediated by DNA methylation at cg10206250.
We performed POO effect association analyses of SNPs with TGs, as well as association analyses of SNPs with DNA methylation probes. These analyses, which were followed by a causal inference test, established that the paternal effect at the SNP rs301621 is induced by treatment and is not mediated by methylation level at cg10206250.
针对甘油三酯（TGs）开展的全基因组关联研究尚未考虑到可能部分解释性状遗传力的表观遗传机制。
在真实的GAW20家系数据集中，针对治疗前TG水平、治疗后TG水平以及治疗前后TG水平差异，采用无假设方法或候选方法进行了亲本来源（POO）效应关联分析。我们检测到22个具有提示性POO效应的遗传变异，涉及至少1种表型（P≤10）。我们评估了这22个显示POO效应的显著遗传变异与与TGs相关的紧密DNA甲基化探针之间的关联。位于这22个单核苷酸多态性（SNP）附近的总共18个DNA甲基化探针与至少1种表型相关，并且6个SNP-探针配对在P<0.05的名义水平上与DNA甲基化探针相关，其中1对呈现出POO效应的证据。我们的分析确定了单核苷酸多态性rs301621对治疗前后TG水平差异的父系效应（P=1.2×10）。同一个单核苷酸多态性显示出对附近一个探针（cg10206250）甲基化水平的母系效应证据（P=0.01）。使用因果推断检验，我们确定观察到的rs301621的POO效应不是由cg10206250处的DNA甲基化介导的。
我们对SNP与TGs进行了POO效应关联分析，以及SNP与DNA甲基化探针的关联分析。这些分析随后进行了因果推断检验，确定了单核苷酸多态性rs301621处的父系效应是由治疗诱导的，而非由cg10206250处的甲基化水平介导。
