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HGG advances · 2026

Large-scale blood pressure GWAS accounting for gene-depression interactions in 564,680 individuals from diverse populations.

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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

Аннотация

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.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты