GWAS Improved BP Polygenic Risk Scores

A single-stage common-variant genome-wide association study (GWAS) of blood pressure (BP) in European-ancestry adults improved BP polygenic risk scores (PRS) and provided additional insights into the genetic contribution of BP. The study identified 113 novel loci, reporting a total of 2,103 independent genetic signals in 1,028,980 European individuals from the meta-analysis of four existing BP-GWAS datasets. These associations explained more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of PRSs revealed clinically meaningful differences in BP (16.9 mmHg systolic BP) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve from 0.791 to 0.826. Comparison of the 2,103 loci results in non-European ancestries showed significant PRS associations in a large African-American sample, although the levels of correlation varied between the comparisons with Japanese versus African ancestries and between novel versus known loci. Secondary analyses implicated 500 genes previously unreported for BP. The findings demonstrate that the biology of BP is highly complex and polygenic and highlight the role of increasingly large genomic studies for precision health research. Source: https://www.nature.com/