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. ### Competing Interest Statement Wei Gan is now an employee of Novo Nordisk Research Centre Oxford Ltd ### Funding Statement This research was funded in whole, or in part, by the Wellcome Trust [212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the Ethical Review Committee of the Chinese Centre for Disease Control and Prevention (Beijing, China, 005/2004) and the Oxford Tropical Research Ethics Committee, University of Oxford (UK, 025-04), and all participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The China Kadoorie Biobank (CKB) is a global resource for the investigation of lifestyle, environmental, blood biochemical and genetic factors as determinants of common diseases. The CKB study group is committed to making the cohort data available to the s cientific community in China, the UK and worldwide to advance knowledge about the causes, prevention and treatment of disease. Full details of what data is currently available to open access users and how to apply for it, visit: . Researchers who are interested in obtaining the raw data from the China Kadoorie Biobank study that underlines this paper should contact ckbaccess{at}ndph.ox.ac.uk. A research proposal will be requested to ensure that any analysis is performed by bona fide researchers and - where data is not currently available to open access researchers - is restricted to the topic covered in this paper.