Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Blood pressure (BP) is a major, heritable determinant of cardiometabolic health. Genome-wide association studies (GWAS) have identified thousands of BP-influencing genetic variants. People of admixed American (AMR) ancestry harbour variants that are rare in other populations yet remain understudied in GWAS. Here, we perform GWAS of four BP traits in 140,559 participants from the Mexico City Prospective Study. Conditional analyses identified 78 independent signals for systolic BP, 61 for diastolic BP, 88 for mean arterial pressure and 24 for pulse pressure. Trans-ancestry meta-analysis externally replicated 13 novel signals, and six more replicated in AMR-ancestry meta-analysis. Overall, we found significant heterogeneity between AMR and other ancestries at nine loci. Functional integration analyses implicated the heart, arterial tree, adrenal glands, and kidney in BP regulation. Analysis of exome-sequenced rare variants identified genes that may act through kidney and endothelial function. The results underscore the value of including diverse populations in genetic discovery.
Source: medRxiv
Authors: Michael Turner, Jaime Berumen, Sam Morris, Diego Aguilar-Ramírez, Luisa Fernández-Chirino, Tin Orešković, Paulina Baca, Elizabeth Barrera, Fernando Rivas, Louisa Gnatiuc Friedrichs, Michael Hill, Eirini Trichia, Alejandra Vergara-Lope, Rachel Wade, Ernst Mayerhofer, Moeen Riaz, Iona Y. Millwood, Robin G. Walters, Alfred Pozarickij, Jerome I. Rotter, Jie Yao, Henry J. Lin, Xiuqing Guo, Natalie Staplin, Pablo Kuri-Morales, Richard Haynes, Jesús Alegre-Díaz, Jonathan R. Emberson, Roberto Tapia-Conyer, Jason M. Torres
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G1261793039, G1276754516, G1539384734, G1640378483, G1803853571, The Mexico City Prospective Study, G1905341482, G2093189309, G2144938473, G22458031, G2283629214, G2334180555, G2580996367, G2774420650, G2837638605, G290884426, G291913881, G3570589137, G3581052147, G3667269547, G370977179, Research Excellence (renewal), G4401650913, G4429312988, G4563812999, G4617978461, G5092239925, G5104865114, G5108002584, G514410172, Infrastructure support for the Mexico City Prospective Study, G5893636606, G5965568373, G6382156846, Institute for Clinical and Translational Research, G6499914542, G66341962, G7606975397, G78770644, G805458286, Clinical and Translational Science Award, Adding to a Mexican-funded questionnaire-based prospective study of cause-specific mortality in 200,000 adults the extra costs of blood sampling and long-term plasma & DNA storage in Oxford for later case-control assays., G8761005068, G991334795
OpenAlex ID: W7213772913
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