biostudies-literatureUnknownHirohama DNIDDK NIH HHSResearch grant from Manpei Suzuki Diabetes FoundationNational Institutes of HealthNearly one-third of the global population is affected by cardio-kidney-metabolic (CKM) diseases; however, the molecular mechanisms underlying CKM diseases are poorly understood. Here we show that tissue proteomics provide critical insights not captured by tissue gene expression or blood proteomics information by performing whole-genome and RNA sequencing and proteomics analysis of human kidney samples (n = 337), and we generated a publicly available database. Via Bayesian co-localization and Mendelian randomization analyses of kidney protein quantitative trait loci and 36 CKM genome-wide association studies, we prioritized 89 proteins for CKM traits. We prioritized relationships that could underlie the interconnectedness of CKM traits and discovered multiple and targetable mechanisms for CNature medicinehttps://www.ebi.ac.uk/biostudies/studies/S-EPMC12435990biostudies-literatureThe proteogenomic landscape of the human kidney and implications for cardio-kidney-metabolic health.PMC12435990R01 DK087635R01 DK123459R01 DK076077R01 DK105821Liu HVitale SNiewczas MALi CFadista JSusztak KZeng LNguyen TOlsson NAbedini AMohandes SLevinsohn JMcAllister FEVassalotti AShungin DKarihaloo AHirohama DHa EfalseThe proteogenomic landscape of the human kidney and implications for cardio-kidney-metabolic health.Nearly one-third of the global population is affected by cardio-kidney-metabolic (CKM) diseases; however, the molecular mechanisms underlying CKM diseases are poorly understood. Here we show that tissue proteomics provide critical insights not captured by tissue gene expression or blood proteomics information by performing whole-genome and RNA sequencing and proteomics analysis of human kidney samples (n = 337), and we generated a publicly available database. Via Bayesian co-localization and Mendelian randomization analyses of kidney protein quantitative trait loci and 36 CKM genome-wide association studies, we prioritized 89 proteins for CKM traits. We prioritized relationships that could underlie the interconnectedness of CKM traits and discovered multiple and targetable mechanisms for C2025-01-01T00:00:00Z2025 Aug2026-06-01T14:00:53.244Z2026-04-08T13:17:08.561ZS-EPMC124359904079693510.1038/s41591-025-03872-8