Division of Genome and Health Big Data, Department of Public Health Sciences Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
Division of Genome and Health Big Data, Department of Public Health Sciences Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
J Lipid Res. 2019 Dec;60(12):2090-2101. doi: 10.1194/jlr.P119000226. Epub 2019 Oct 29.
Dyslipidemia is a well-established risk factor for CVD. Studies suggest that similar fat accumulation in a given population might result in different levels of dyslipidemia risk among individuals; for example, despite similar or leaner body composition compared with Caucasians, Asians of Korean descent experience a higher prevalence of dyslipidemia. These variations imply a possible role of gene-obesity interactions on lipid profiles. Genome-wide association studies have identified more than 500 loci regulating plasma lipids, but the interaction structure between genes and obesity traits remains unclear. We hypothesized that some loci modify the effects of obesity on dyslipidemia risk and analyzed extensive gene-environment interactions (G×Es) at genome-wide levels to search for replicated gene-obesity interactive SNPs. In four Korean cohorts (n = 18,025), we identified and replicated 20 gene-obesity interactions, including novel variants ( and ) and known lipid-associated variants (, , , and ). When we estimated the additional heritability of dyslipidemia by considering G×Es, the gain was substantial for triglycerides (TGs) but mild for LDL cholesterol (LDL-C) and total cholesterol (Total-C); the interaction explained up to 18.7% of TG, 2.4% of LDL-C, and 1.9% of Total-C heritability associated with waist-hip ratio. Our findings suggest that some individuals are prone to develop abnormal lipid profiles, particularly with regard to TGs, even with slight increases in obesity indices; ethnic diversities in the risk alleles might partly explain the differential dyslipidemia risk between populations. Research about these interacting variables may facilitate knowledge-based approaches to personalize health guidelines according to individual genetic profiles.
血脂异常是 CVD 的一个既定危险因素。研究表明，在给定人群中相似的脂肪堆积可能导致个体之间不同程度的血脂异常风险；例如，与高加索人相比，尽管具有相似或更苗条的身体组成，但韩国裔亚洲人血脂异常的患病率更高。这些差异表明基因-肥胖相互作用可能对脂质谱有一定的作用。全基因组关联研究已经确定了 500 多个调节血浆脂质的基因座，但基因和肥胖特征之间的相互作用结构仍不清楚。我们假设一些基因座可以改变肥胖对血脂异常风险的影响，并在全基因组水平上分析广泛的基因-环境相互作用（G×E），以寻找复制的基因-肥胖相互作用 SNP。在四个韩国队列（n=18025）中，我们鉴定和复制了 20 个基因-肥胖相互作用，包括新的变体（和）和已知的与脂质相关的变体（、、、和）。当我们通过考虑 G×E 来估计血脂异常的额外遗传度时，甘油三酯（TGs）的增益是显著的，但 LDL 胆固醇（LDL-C）和总胆固醇（Total-C）的增益是温和的；这种相互作用解释了高达 18.7%的 TG、2.4%的 LDL-C 和 1.9%的腰围-臀围比与总胆固醇相关的遗传度。我们的研究结果表明，一些人更容易出现异常的脂质谱，特别是甘油三酯，即使肥胖指数略有增加；风险等位基因的种族差异可能部分解释了不同人群之间血脂异常风险的差异。对这些相互作用变量的研究可能有助于根据个体的遗传特征，为个人制定基于知识的健康指南。
