| Shrnutí: | <p><b>Introduction</b> Elevated blood pressure is the leading cause of disability-adjusted life years lost globally, but most studies of its determinants and effects are in high-income populations of European ancestry.</p>
<p><b>Methods</b> The Mexico City Prospective Study (MCPS) recruited 159 775 participants aged >35 years between 1998 and 2004. Follow-up is via the national mortality register. Genetic data for ~140 00 participants has been generated.</p>
<p>Haplotype-based principal components (PCs) were generated with IMPUTE5 and compared to genotype-based PCs. Genome-wide association studies (GWAS) of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were conducted using SUGEN and conditionally-independent signals identified with a forwards-selection-backwards-elimination algorithm. Enrichment analyses were conducted with GARFIELD. Mendelian randomization (MR) analyses were conducted using trans-ancestry SBP and DBP genetic scores and the ratio method and compared to conventional epidemiological analyses.</p>
<p><b>Results</b> Haplotype-based PCs delineated prevalent ancestries at lower dimensionality than genotype-based PCs in an unrelated sub-sample. However, they could not be effectively applied to the whole cohort.</p>
<p>GWAS of SBP, DBP, MAP and PP identified 71 signals at 66 loci, 53 signals at 52 loci, 74 signals at 71 loci and 24 signals at 24 loci, respectively. Meta-analysis of external summary statistics replicated 2/14, 0/15, 3/21 and 1/2 novel signals for SBP, DBP, MAP and PP respectively. GARFIELD identified endothelium and renal tract as more likely to harbour GWAS-significant variants.</p>
<p>MR estimates of the SBP and DBP‘s effects on premature cardiovascular mortality were approximately twice as strong as conventional estimates, reflecting the life-course nature of genetic exposures. SBP may cause kidney disease, but more events are needed.</p>
<p><b>Conclusions</b> MCPS harbours novel blood pressure associations, but replication in more Latin American-ancestry cohorts is required. Lowering blood pressure continues to offer large benefits to population health and should remain a key public health focus.</p>
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