Polygenic risk scores associate with blood pressure traits across the lifespan
Øvretveit, Karsten; Ingeström, Emma Maria Lovisa; Spitieris, Michail; Tragante, Vinicius; Wade, Kaitlin Hazel; Thomas, Laurent Francois; Wolford, Brooke Nichole; Wisløff, Ulrik; Gudbjartsson, Daníel Fannar; Hólm, Hilma Asbjørn; Stefánsson, Kári; Brumpton, Ben Michael; Hveem, Kristian
Peer reviewed, Journal article
Published version
Permanent lenke
https://hdl.handle.net/11250/3108374Utgivelsesdato
2023Metadata
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Originalversjon
10.1093/eurjpc/zwad365Sammendrag
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.