Genetic analyses of blood pressure traits in 140,000 admixed adults from Mexico City

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.