| Title: |
Large-Scale Blood Pressure Gwas Accounting for Gene-Depression Interactions in 564,680 Individuals From Diverse Populations |
| Authors: |
Lee, Songmi; Miller, Clint L; Bentley, Amy R; Brown, Michael R; Nagarajan, Pavithra; Noordam, Raymond; Morrison, John L; Schwander, Karen; Westerman, Kenneth; Kho, Minjung; Kraja, Aldi T; de Vries, Paul S; Ammous, Farah; Aschard, Hughes; Bartz, Traci M; Do, Anh; Dupont, Charles T; Feitosa, Mary F; Gudmundsdottir, Valborg; Guo, Xiuqing; Harris, Sarah E; Hikino, Keiko; Huang, Zhijie; Lefevre, Christophe; Lyytikäinen, Leo-Pekka; Milaneschi, Yuri; Nardone, Giuseppe Giovanni; Santin, Aurora; Schmidt, Helena; Shen, Botong; Sofer, Tamar; Sun, Quan; Tan, Ye An; Tang, Jingxian; Thériault, Sébastien; van der Most, Peter J; Ware, Erin B; Weiss, Stefan; Xing, Wang Ya; Yu, Chenglong; Zhao, Wei; Ansari, Md Abu Yusuf; Anugu, Pramod; Attia, John R; Bazzano, Lydia A; Bis, Joshua C; Breyer, Max; Cade, Brian; Chen, Guanjie; Collins, Stacey; Corley, Janie; Davies, Gail; Dörr, Marcus; Du, Jiawen; Edwards, Todd L; Faquih, Tariq; Faul, Jessica D; Fohner, Alison E; Fretts, Amanda M; Gangireddy, Srushti; Gepner, Adam; Graff, MariaElisa; Hofer, Edith; Homuth, Georg; Hood, Michelle M; Jie, Xu; Kähönen, Mika; Kardia, Sharon L R; Karvonen-Gutierrez, Carrie A; Launer, Lenore J; Levy, Daniel; Maheshwari, Maitreiyi; Martin, Lisa W; Matsuda, Koichi; McNeil, John J; Nolte, Ilja M; Okochi, Tomo; Raffield, Laura M; Raitakari, Olli T; Risch, Lorenz; Risch, Martin; Roux, Ana Diez; Ruiz-Narvaez, Edward A; Russ, Tom C; Saito, Takeo; Schreiner, Pamela J; Scott, Rodney J; Shikany, James; Smith, Jennifer A; Snieder, Harold; Spedicati, Beatrice; Tai, E Shyong; Taylor, Adele M; Taylor, Kent D; Tesolin, Paola; van Dam, Rob M; Wang, Rujia; Wenbin, Wei; Xie, Tian; Yao, Jie; Young, Kristin L; Zhang, Ruiyuan; Zonderman, Alan B; Biobank Japan Project; Lifelines Cohort Study; Concas, Maria Pina; Conen, David; Cox, Simon R; Evans, Michele K; Fox, Ervin R; de Las Fuentes, Lisa; Giri, Ayush; Girotto, Giorgia; Grabe, Hans J; Gu, Charles; Gudnason, Vilmundur; Harlow, Sioban D; Holliday, Elizabeth; Jost, Jonas B; Lacaze, Paul; Lee, Seunggeun; Lehtimäki, Terho; Li, Changwei; Liu, Ching-Ti; Morrison, Alanna C; North, Kari E; Penninx, Brenda W J H; Peyser, Patricia A; Province, Michael M; Psaty, Bruce M; Redline, Susan; Rosendaal, Frits R; Rotimi, Charles N; Rotter, Jerome I; Schmidt, Reinhold; Sim, Xueling; Terao, Chikashi; Weir, David R; Zhu, Xiaofeng; Franceschini, Nora; O'Connell, Jeffrey R; Jaquish, Cashell E; Wang, Heming; Manning, Alisa; Munroe, Patricia B; Rao, Dabeeru C; Chen, Han; Gauderman, W James; Bierut, Laura J; Winkler, Thomas W; Fornage, Myriam |
| Source: |
Faculty, Staff and Student Publications |
| Publisher Information: |
DigitalCommons@TMC |
| Publication Year: |
2026 |
| Collection: |
Houston Academy of Medicine-Texas Medical Center (HAM-TMC): DigitalCommons@The Texas Medical Center |
| Subject Terms: |
blood pressure; depressive symptomatology; gene-environment interactions; genetics; genome-wide association study; hypertension; multi-ancestry; Medicine and Health Sciences; Public Health |
| Description: |
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. |
| Document Type: |
text |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://digitalcommons.library.tmc.edu/uthsph_docs/1221; https://digitalcommons.library.tmc.edu/context/uthsph_docs/article/2175/viewcontent/PIIS2666247726000060_compressed.pdf |
| DOI: |
10.1016/j.xhgg.2026.100566 |
| Availability: |
https://digitalcommons.library.tmc.edu/uthsph_docs/1221; https://doi.org/10.1016/j.xhgg.2026.100566; https://digitalcommons.library.tmc.edu/context/uthsph_docs/article/2175/viewcontent/PIIS2666247726000060_compressed.pdf |
| Accession Number: |
edsbas.94A3706 |
| Database: |
BASE |