Li Xin, Guo Yu, Liang Haihai, Wang Jinghao, Qi Lishuang
The Sino-Russian Medical Research Center of Jinan University, The Institute of Chronic Disease of Jinan University, The First Affiliated Hospital of Jinan University, Guangzhou, 511436, China.
School of Computer Science and Technology, Harbin Institute of Technology, Harbin, 150086, China.
Sci Rep. 2024 Aug 1;14(1):17792. doi: 10.1038/s41598-024-68751-7.
Hypertension is a disease associated with epigenetic aging. However, the pathogenic mechanism underlying this relationship remains unclear. We aimed to characterize the shared genetic architecture of hypertension and epigenetic aging, and identify novel risk loci. Leveraging genome-wide association studies (GWAS) summary statistics of hypertension (129,909 cases and 354,689 controls) and four epigenetic clocks (N = 34,710), we investigated genetic architectures and genetic overlap using bivariate casual mixture model and conditional/conjunctional false discovery rate methods. Functional gene-sets pathway analyses were performed by functional mapping and gene annotation (FUMA) protocol. Hypertension was polygenic with 2.8 K trait-influencing genetic variants. We observed cross-trait genetic enrichment and genetic overlap between hypertension and all four measures of epigenetic aging. Further, we identified 32 distinct genomic loci jointly associated with hypertension and epigenetic aging. Notably, rs1849209 was shared between hypertension and three epigenetic clocks (HannumAge, IEAA, and PhenoAge). The shared loci exhibited a combination of concordant and discordant allelic effects. Functional gene-set analyses revealed significant enrichment in biological pathways related to sensory perception of smell and nervous system processes. We observed genetic overlaps with mixed effect directions between hypertension and all four epigenetic aging measures, and identified 32 shared distinct loci with mixed effect directions, 25 of which were novel for hypertension. Shared genes enriched in biological pathways related to olfaction.
高血压是一种与表观遗传衰老相关的疾病。然而，这种关系背后的致病机制仍不清楚。我们旨在描述高血压和表观遗传衰老的共同遗传结构，并确定新的风险位点。利用高血压（129,909例病例和354,689例对照）和四个表观遗传时钟（N = 34,710）的全基因组关联研究（GWAS）汇总统计数据，我们使用双变量因果混合模型和条件/联合错误发现率方法研究了遗传结构和遗传重叠。通过功能映射和基因注释（FUMA）协议进行功能基因集通路分析。高血压是多基因的，有2800个影响性状的遗传变异。我们观察到高血压与所有四种表观遗传衰老指标之间存在跨性状遗传富集和遗传重叠。此外，我们确定了32个与高血压和表观遗传衰老共同相关的不同基因组位点。值得注意的是，rs1849209在高血压和三个表观遗传时钟（HannumAge、IEAA和PhenoAge）之间共享。共享位点表现出一致和不一致等位基因效应的组合。功能基因集分析显示，在与嗅觉感知和神经系统过程相关的生物通路中存在显著富集。我们观察到高血压与所有四种表观遗传衰老指标之间存在混合效应方向的遗传重叠，并确定了32个具有混合效应方向的共享不同位点，其中25个是高血压的新位点。共享基因在与嗅觉相关的生物通路中富集。
