Circulating Cardiovascular Proteomic Associations With Genetics and Disease

作者：Kathryn A. McGurk, Lara Curran, Arunashis Sau, Fu Siong Ng, Brian P. Halliday, James S. Ware, Declan P. O’Regan · 发表于：Circulation Genomic and Precision Medicine · 年份：2025 · DOI：10.1161/circgen.124.005005 · 被引用次数：2 · 研究领域：Renin-Angiotensin System Studies、Genetics and Physical Performance、GDF15 and Related Biomarkers

BACKGROUND: The analysis of the circulating proteome can identify translational modifiers and biomarkers of disease expressivity and severity at a given time point. Here, we explore the relationships between protein measures implicated in cardiovascular disease and whether they mediate causal relationships between cardiovascular risk factors and disease development. METHODS: To understand the relationships between circulating biomarkers and genetic variants, medications, anthropometric traits, lifestyle factors, imaging-derived measures, and diagnoses of cardiovascular disease, we undertook in-depth analyses of measures of 9 plasma proteins with a priori roles in genetic and structural cardiovascular disease or treatment pathways (ACE2 [angiotensin-converting enzyme 2], ACTA2 [actin alpha 2], ACTN4 [actinin alpha 4], BAG3 [BAG cochaperone 3], BNP [B-type natriuretic peptide], CDKN1A [cyclin-dependent kinase inhibitor 1A], NOTCH1 [neurogenic locus notch homolog protein 1], NT-proBNP [N-terminal pro-B-type natriuretic peptide], and TNNI3 [troponin I]) from the Pharma Proteomics Project of the UK Biobank cohort (over 45 000 participants sampled at recruitment). RESULTS: We identified significant variability in circulating proteins with age, sex, ancestry, alcohol intake, smoking, and medication intake. Phenome-wide association studies highlighted the range of cardiovascular clinical features with relationships to protein levels. Genome-wide genetic association studies identified...