Circulating proteins are the result of genetically inherited predispositions to diseases and the influences of environmental exposures, diet, lifestyle behaviours and the ageing process.1 This dual capacity of proteins to reflect both genetic and environmental factors is crucial for understanding and stratifying risks for common complex diseases like cardiometabolic disorders. The emergence of high-throughput proteomics has transformed our ability to study the association between circulating protein levels and both existing and emerging diseases on a large scale. In addition to providing new insights into disease mechanisms, proteomics facilitates the identification and validation of biomarkers for diagnosing diseases, predicting prognosis and assessing treatment responses. This paves the way for more personalised approaches to disease prevention and treatment.2

Wu and colleagues3 conducted a systematic review and meta-analysis, examining a variety of observational studies and Mendelian randomisation (MR) studies involving over 26 million non-overlapping participants. Their research focused on the link between the circulating proteome and cardiometabolic diseases (CMD), such as coronary heart disease, stroke, type 2 diabetes, heart failure, atrial fibrillation and atherosclerosis. Overall, 560 proteins were observationally associated with CMD, while 245 proteins showed genetic associations. Among these proteins, 133 in the observational studies and 23 in the MR studies showed pleiotropic effects, being associated with multiple CMD. Of the 291 protein–disease pairs examined, 22 showed directionally consistent associations across both estimates. Additionally, among these protein–disease pairs, 288 proteins were identified as putative causal biomarkers yet lacked evidence of being explored in drug development, highlighting their potential as new therapeutic targets. …