Comprehensive investigation of circulating biomarkers and their causal role in atherosclerosis-related risk factors and clinical events

Background: Circulating biomarkers have been previously associated with atherosclerosis-related risk factors, but the nature of these associations is incompletely understood.

Methods: We performed multivariable-adjusted regressions and 2-sample Mendelian randomization analyses to assess observational and causal associations of 27 circulating biomarkers with 7 cardiovascular traits in up to 451 933 participants of the UK Biobank.

Results: After multiple-testing correction (alpha=1.3Å~10−4), we found a total of 15, 9, 21, 22, 26, 24, and 26 biomarkers strongly associated with coronary artery disease, ischemic stroke, atrial fibrillation, type 2 diabetes, systolic blood pressure, body mass index, and waist-to-hip ratio; respectively. The Mendelian randomization analyses confirmed strong evidence of previously suggested causal associations for several glucose- and lipid-related biomarkers with type 2 diabetes and coronary artery disease. Particularly interesting findings included a pr...