Summary
A genome-wide association study of 140,559 adults from the Mexico City Prospective Study identified 78 independent signals for systolic blood pressure and hundreds more for other blood pressure traits, including variants rare in other populations.
A genome-wide association study (GWAS) of blood pressure traits in 140,559 adults from the Mexico City Prospective Study has identified hundreds of new genetic signals, many of which are rare or absent in other populations. The preprint, posted on medRxiv on 20 September 2026, highlights the value of studying admixed American (AMR) ancestry, where the genetic variants influencing blood pressure remain poorly characterised.
Contents
Study design and population
Blood pressure is a highly heritable risk factor for cardiovascular and renal disease. Previous GWAS have identified thousands of common variants associated with blood pressure, but most have been conducted in populations of European ancestry. People of admixed American ancestry—those with mixed Indigenous American, European, and African ancestry—harbour variants that are rare in other populations yet are underrepresented in genetic research.
The Mexico City Prospective Study is a long-running cohort of adults from Mexico City. For this analysis, the researchers performed GWAS of four blood pressure traits: systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP). The study included 140,559 participants, making it one of the largest GWAS of admixed American ancestry to date. Ethics approval was obtained from Mexican and Oxford University authorities, and all participants provided informed consent.
Key findings
Conditional analyses identified 78 independent signals for SBP, 61 for DBP, 88 for MAP, and 24 for PP. To validate these signals, the researchers conducted trans-ancestry meta-analysis with external studies. Thirteen novel signals were externally replicated, and a further six replicated in an AMR-ancestry meta-analysis, confirming that many of the new associations are not false positives.
At nine loci, the researchers found significant heterogeneity between the AMR cohort and other ancestries, suggesting that genetic effects on blood pressure may differ across populations. Functional integration analyses—which combine genetic data with gene expression, chromatin interaction, and other regulatory information—implicated the heart, arterial tree, adrenal glands, and kidney in blood pressure regulation. These organs are known to play central roles in pressure homeostasis, and the findings reinforce their importance.
The study also examined rare variants through exome sequencing. This analysis identified genes that may act through kidney and endothelial function, offering potential new avenues for therapeutic development. However, these rare-variant associations are preliminary and require further validation.
Significance and limitations
This study demonstrates that large-scale genetic analysis of admixed American populations can uncover variants that are missed in studies of European or other ancestries. By identifying hundreds of new blood pressure signals, the work expands the catalogue of genetic loci influencing a major determinant of cardiometabolic health. The results also highlight the biological pathways involved, which may inform future drug targets and risk prediction tools.
Several caveats apply. The preprint has not yet undergone peer review, so the findings should be interpreted with caution. The functional implications are based on computational integration and have not been experimentally confirmed. The cohort is drawn from Mexico City, which may limit generalisability to other admixed American populations or to Indigenous communities with different genetic backgrounds. Finally, the clinical utility of the new genetic signals—for example, in risk stratification or personalised treatment—remains to be established in prospective studies.
Despite these limitations, the study underscores the importance of including diverse populations in genetic discovery. As GWAS expand globally, the insights gained from admixed cohorts like this one are likely to improve our understanding of blood pressure biology and its translation into clinical practice.