Faculty, Staff and Student Publications
Language
English
Publication Date
1-10-2026
Journal
Human Genetics and Genomics Advances
DOI
10.1016/j.xhgg.2026.100566
PMID
41520179
Abstract
Gene-environment interactions may enhance our understanding of blood pressure (BP) biology. We conducted a meta-analysis of multi-population genome-wide association studies (GWASs) of BP traits accounting for gene-depressive symptomatology (DEPR) interactions. Our study included 564,680 adults from 67 cohorts and four population backgrounds: African (5%), Asian (7%), European (85%), and Hispanic (3%). We discovered seven previously unreported BP loci showing gene-DEPR interaction. These loci mapped to genes implicated in neurogenesis (TGFA and CASP3), lipid metabolism (ACSL1), neuronal apoptosis (CASP3), and synaptic activity (CNTN6 and DBI). We also showed evidence for gene-DEPR interaction at nine known BP loci, further suggesting links between mood disturbance and BP regulation. Of the 16 identified loci, 11 were derived from non-European populations. Post-GWAS analyses prioritized 36 genes, including genes involved in synaptic functions (DOCK4 and MAGI2) and neuronal signaling (CCK, UGDH, and SLC01A2). Integrative druggability analyses identified 11 druggable candidate gene targets linked to pathways involved in mood disorders as well as known anti-hypertensive drugs. Our findings emphasize the importance of considering gene-DEPR interactions on BP, particularly in non-European populations. Our prioritized genes and druggable targets highlight biological pathways connecting mood disorders and hypertension and suggest opportunities for BP drug repurposing and risk factor prevention, especially in individuals with DEPR.
Keywords
blood pressure, depressive symptomatology, gene-environment interactions, genetics, genome-wide association study, hypertension, multi-ancestry
Published Open-Access
yes
Recommended Citation
Lee, Songmi; Miller, Clint L; Bentley, Amy R; et al., "Large-Scale Blood Pressure Gwas Accounting for Gene-Depression Interactions in 564,680 Individuals From Diverse Populations" (2026). Faculty, Staff and Student Publications. 1221.
https://digitalcommons.library.tmc.edu/uthsph_docs/1221