The AGT epistasis pattern proposed a novel role for ZBED9 in regulating blood pressure: Tehran Cardiometabolic genetic study (TCGS)
The AGT epistasis pattern proposed a novel role for ZBED9 in regulating blood pressure: Tehran Cardiometabolic genetic study (TCGS)
复制标题
DOI：
10.1016/j.gene.2022.146560
复制
发表时间：
2022-05-18
期刊：
影响因子：
3.5
通讯作者：
Daneshpour, Maryam S.
中科院分区：
文献类型：
--
作者：
Akbarzadeh, Mahdi;Riahi, Parisa;Daneshpour, Maryam S.
前言：高血压被广泛认为是心血管疾病最重要的危险因素。上位性分析可能为高血压的遗传基础提供更多的洞察力。方法：采用嵌套式病例对照设计，对4214名德黑兰心脏代谢遗传学研究(TCGS)的成人进行研究，评估65个先前相关基因的SNPs，包括ZBED9、AGT和TNXB。利用基于序列的核关联检验(SKAT)确定每个基因的整合效应。我们使用基于模型的多因素降维(Mb-MDR)和基于熵的基因-基因互作(IGENT)方法来确定交互作用和上位性模式。结果：各基因的综合效应与血压性状有统计学意义的相关性(P值和t；0.05)。单基因座分析发现ZBED9(Rs450630)和AGT(Rs4762)的两个错义变异与高血压有关。在ZBED9基因中，发现了显著的局部相互作用。Rs450630的G等位基因对高血压有拮抗作用，但有趣的是，IGENT分析显示ZBED9、AGT和TNXB基因座的不同组合对高血压有显著的上位性效应。结论：我们发现高血压必需基因(AGT)的显著变异和ZBED9的错义变异之间存在新的交互作用，这使得我们的研究重点转向ZBED9和S在血压调节中的作用。
Introduction: High blood pressure is widely regarded as the most important risk factor for cardiovascular diseases. Epistasis analysis may provide additional insight into the genetic basis of hypertension. Methods: A nested case-control design was used on 4214 unrelated Tehran Cardiometabolic Genetic Study (TCGS) adults to evaluate 65 SNPs of previously associated genes, including ZBED9, AGT, and TNXB. The integrated effect of each gene was determined using the Sequence-based Kernel Association Test (SKAT). We used model based multifactor dimension reduction (Mb-MDR) and entropy-based gene-gene interaction (IGENT) methods to determine interaction and epistasis patterns. Results: The integrated effect of each gene has a statistically significant association with blood pressure traits (P value < 0.05). The single-locus analysis identified two missense variants in ZBED9 (rs450630) and AGT (rs4762) associated with hypertension. In the ZBED9 gene, significant local interactions were discovered. The G allele in rs450630 showed an antagonistic effect on hypertension, but interestingly, IGENT analysis revealed significant epistasis effects for different combinations of ZBED9, AGT, and TNXB loci. Conclusion: We discovered a novel interaction effect between a significant variant in an essential gene for hypertension (AGT) and a missense variant in ZBED9, which has shifted our focus to ZBED9 & PRIME;s role in blood pressure regulation.