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Genome-wide association analysis of hypertension and epigenetic aging reveals shared genetic architecture and identifies novel risk loci

表观遗传学 遗传建筑学 全基因组关联研究 遗传学 遗传关联 生物 联想(心理学) 计算生物学 生物信息学 基因 单核苷酸多态性 数量性状位点 基因型 心理学 心理治疗师
作者
Xin Li,Yu Guo,Haihai Liang,Jinghao Wang,Lishuang Qi
出处
期刊:Scientific Reports [Nature Portfolio]
卷期号:14 (1)
标识
DOI:10.1038/s41598-024-68751-7
摘要

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.
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