Causal relevance of different blood pressure traits on risk of cardiovascular diseases: GWAS and Mendelian randomisation in 100,000 Chinese adults

Elevated blood pressure (BP) is major risk factor for cardiovascular diseases (CVD). Genome-wide association studies (GWAS) conducted predominantly in populations of European ancestry have identified >2,000 BP-associated loci, but other ancestries have been less well-studied. We conducted GWAS of systolic, diastolic, pulse, and mean arterial BP in 100,453 Chinese adults. We identified 128 non-overlapping loci associated with one or more BP traits, harbouring 81 novel associations. Despite strong genetic correlations between populations, we identified appreciably higher heritability and larger variant effect sizes in Chinese compared with European or Japanese ancestry populations. Using instruments derived from these GWAS, multivariable Mendelian randomisation demonstrated strong causal associations of specific BP traits with CVD, including systolic BP with intracranial haemorrhage, and pulse pressure with carotid plaque. The findings reinforce the need for studies in diverse populations to understand the genetic determinants of BP traits and their role in disease risk.