Polygenic risk scores associate with blood pressure traits across the lifespan.

AIMS: Hypertension is a major modifiable cause of morbidity and mortality that affects over 1 billion people worldwide. Blood pressure (BP) traits have a strong genetic component that can be quantified with polygenic risk scores (PRSs). To date, the performance of BP PRSs has mainly been assessed in adults, and less is known about polygenic hypertension risk in childhood. METHODS AND RESULTS: Multiple PRSs for systolic BP (SBP), diastolic BP (DBP), and pulse pressure were developed using either genome-wide significant weights, pruning and thresholding, or Bayesian regression. Among 87 total PRSs, the top performer for each trait was applied in independent cohorts of children and adult to assess genotype-phenotype associations and disease risk across the lifespan. Differences between those with low (1st decile), average (2nd-9th decile), and high (10th decile) PRS emerge in the first years of life and are maintained throughout adulthood. These diverging BP trajectories also seem to affect cardiovascular and renal disease risk, with increased risk observed among those in the top decile and reduced risk among those in the bottom decile of the polygenic risk distribution compared with the rest of the population. CONCLUSION: Genetic risk factors are associated with BP traits across the lifespan, beginning in the first years of life. Given the importance of exposure time in disease pathogenesis and the early rise in BP levels among those genetically susceptible, PRSs may help identify high-risk individuals prior to hypertension onset, facilitate primordial prevention, and reduce the burden of this public health challenge.

A high genetic risk of elevated blood pressure (BP) is associated with increased BP from early childhood and throughout the lifespan. Inherited predispositions also affect the risk of cardiovascular morbidity and mortality, yet this appears to be modified by the absence or presence of hypertension, indicating that genetic hypertension risk is not deterministic, and that controlling BP can and should be done across the polygenic risk distribution. Given that differences in BP emerge early in life as a function of genetic risk, polygenic risk scores have the potential to reduce the duration of exposure to high BP by identifying high-risk individuals from birth, and thereby attenuate lifelong disease risk.

Polygenic Interactions With Environmental Exposures in Blood Pressure Regulation: The HUNT Study.

BACKGROUND: The essential hypertension phenotype results from an interplay between genetic and environmental factors. The influence of lifestyle exposures such as excess adiposity, alcohol consumption, tobacco use, diet, and activity patterns on blood pressure (BP) is well established. Additionally, polygenic risk scores for BP traits are associated with clinically significant phenotypic variation. However, interactions between genetic and environmental risk factors in hypertension morbidity and mortality are poorly characterized. METHODS AND RESULTS: We used genotype and phenotype data from up to 49 234 participants from the HUNT (Trøndelag Health Study) to model gene-environment interactions between genome-wide polygenic risk scores for systolic BP and diastolic BP and 125 environmental exposures. Among the 125 environmental exposures assessed, 108 and 100 were independently associated with SBP and DBP, respectively. Of these, 12 interactions were identified for genome-wide PRSs for systolic BP and 4 for genome-wide polygenic risk scores for diastolic BP, 2 of which were overlapping (P < 2 × 10-4). We found evidence for gene-dependent influence of lifestyle factors such as cardiorespiratory fitness, dietary patterns, and tobacco exposure, as well as biomarkers such as serum cholesterol, creatinine, and alkaline phosphatase on BP. CONCLUSIONS: Individuals that are genetically susceptible to high BP may be more vulnerable to common acquired risk factors for hypertension, but these effects appear to be modifiable. The gene-dependent influence of several common acquired risk factors indicates the potential of genetic data combined with lifestyle assessments in risk stratification, and gene-environment-informed risk modeling in the prevention and management of hypertension.