Lim Ji Eun, Kim Hye Ok, Rhee Sang Youl, Kim Mi Kyung, Kim Yeon-Jung, Oh Bermseok
Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
Genet Epidemiol. 2019 Jun;43(4):402-413. doi: 10.1002/gepi.22195. Epub 2019 Feb 15.
Hypertension is a complex disorder caused by genetic and environmental risk factors. Recently, genome-wide association studies (GWASs) identified more than 100 genetic variants for blood pressure traits and hypertension. However, the interactions between these genetic variants and environmental factors have not been systematically investigated. Therefore, we examined the interaction between genetic and environmental risk factors in blood pressure traits using the genetic risk score (GRS). Two Korean community-based cohorts, Cohort I (KARE; N = 8,840) and Cohort II (CAVAS; N = 9,599), were used for this study, and GRSs were calculated from 42 GWAS single-nucleotide polymorphisms (SNPs) that were validated for their association in these cohorts. We calculated GRSs in both ways by considering the effect sizes of each SNP (weighted GRS) and not considering the effect sizes (unweighted GRS). The unweighted GRS was strongly associated with systolic blood pressure, diastolic blood pressure, and hypertension (p = 9.03 × 10 , p = 9.41 × 10 , and p = 3.22 × 10 by meta-analysis, respectively) and the weighted GRS showed the similar results. The environmental factors of body mass index, waist circumference, and drinking status were significantly associated with blood pressure traits, and the interaction between these factors and GRSs were examined. However, no interactions were found with either the GRS or the individual SNPs considered for the GRS. Our findings show that it is challenging to find GRS-environment interactions regarding blood pressure traits.
高血压是一种由遗传和环境风险因素引起的复杂疾病。最近,全基因组关联研究(GWAS)确定了100多个与血压性状和高血压相关的基因变异。然而,这些基因变异与环境因素之间的相互作用尚未得到系统研究。因此,我们使用遗传风险评分(GRS)研究了血压性状中遗传和环境风险因素之间的相互作用。本研究使用了两个基于韩国社区的队列,队列I(韩国农村基因组学和流行病学研究;N = 8840)和队列II(心血管疾病与衰老研究;N = 9599),并根据42个在这些队列中经验证具有关联性的GWAS单核苷酸多态性(SNP)计算GRS。我们通过考虑每个SNP的效应大小(加权GRS)和不考虑效应大小(未加权GRS)这两种方式来计算GRS。未加权GRS与收缩压、舒张压和高血压密切相关(通过荟萃分析,p分别为9.03×10 、9.41×10 和3.22×10 ),加权GRS也显示出类似结果。体重指数、腰围和饮酒状况等环境因素与血压性状显著相关,并对这些因素与GRS之间的相互作用进行了研究。然而,并未能发现这些因素与GRS或构成GRS的单个SNP之间存在相互作用。我们的研究结果表明,在血压性状方面寻找GRS与环境的相互作用具有挑战性。