Genetic and Environmental Contributions to Blood Pressure and Kidney Function

Hypertension affects more than 30% of individuals worldwide and is a leading risk factor for cardiovascular disease, morbidity, and mortality. This complex trait is influenced by the interplay between genetic and environmental factors; however, it remains unclear to what extent modifiable lifestyle factors can offset or exacerbate genetic risk. The kidneys play a central role in blood pressure regulation, and impaired renal function can both cause and be caused by elevated blood pressure. Understanding the genetic and environmental determinants of blood pressure and kidney function can therefore provide complementary insights into disease etiology and inform public health and personalized medicine strategies.

This thesis evaluates genetic and environmental factors, and their interactions, on blood pressure, hypertension, and kidney function using two independent cohorts: the Health Workers Cohort Study (HWCS) in Mexico and the Lifelines Cohort Study (Lifelines) in the Netherlands.

This thesis provides new insights into genetic and environment factors that affect blood pressure and kidney function in Mexican and Dutch populations. Identifying genes within biological pathways and gene-gene interaction networks proves useful for selecting candidate SNPs for complex traits. Metabolic markers, such as the TyG index, may serve as early indicators of hypertension risk. Genetic risk scores and polygenic risk scores (PRS) help predict gene-environment interactions, with lifestyle factors modestly amplifying genetic predisposition. Finally, GWAS of creatinine clearance reveals novel variants, including female-specific loci, highlighting CrCl as a complementary phenotype for kidney function studies.