Causal relevance of different blood pressure traits on risk of cardiovascular diseases: GWAS and Mendelian randomisation in 100,000 Chinese adults
Alfred Pozarickij, Wei Gan, Kuang Lin, Robert Clarke, Zammy Fairhurst-Hunter, Masaru Koido, Masahiro Kanai, Yukinori Okada, Yoichiro Kamatani, Derrick Bennett, Huaidong Du, Yiping Chen, Ling Yang, Daniel Avery, Canqing Yu, Min Yu, Canqing Yu, Dan Schmidt Valle, Jun Lv, Junshi Chen, Richard Peto, Rory Collins, Liming Li, Zhengming Chen, Iona Y. Millwood, Robin Walters, China Kadoorie Biobank Collaborative Group
Abstract
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, including 74 newly-reported 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 that BP traits contribute differently to the causal associations of BP with CVD. In particular, only pulse pressure was independently causally associated with carotid plaque. These findings reinforce the need for studies in diverse populations to understand the genetic determinants of BP traits and their roles in disease risk.