{"doi":"10.1101/2023.07.25.23293136","title":"Plasma proteomic signatures of adiposity are associated with cardiovascular risk factors and type 2 diabetes risk in a multi-ethnic Asian population","abstract":"Abstract The molecular mechanisms connecting obesity and cardiometabolic diseases are not fully understood. We evaluated the associations between body mass index (BMI), waist circumference (WC), and ∼5,000 plasma proteins in the Singapore Multi-Ethnic Cohort (MEC1). Among 410 BMI-associated and 385 WC-associated proteins, we identified protein signatures of BMI and WC and validated them in an independent dataset across two timepoints and externally in the Atherosclerosis Risk in Communities (ARIC) study. The BMI- and WC-protein signatures were highly correlated with total and visceral body fat, respectively. Furthermore, the protein signatures were significantly associated with cardiometabolic risk factors and were able to differentiate between metabolically healthy and unhealthy obesity. In prospective analyses, the protein signatures were strongly associated with type 2 diabetes risk in MEC1 (odds ratio per SD increment in WC-protein signature = 2.84, 95% CI 2.47 to 3.25) and ARIC (hazard ratio = 1.97, 95% CI 1.87 to 2.07). Pathways related to cell signaling, systemic inflammation, and glucose and fat metabolism were overrepresented in the BMI- and WC-protein signatures. Our protein signatures have potential uses for the monitoring of metabolically unhealthy obesity. Article Highlights We evaluated the associations between ∼5000 plasma proteins and BMI and WC in a multi-ethnic Asian population. We identified 410 proteins associated with BMI and 385 proteins associated with WC and derived protein signatures of BMI and WC, which we validated externally in a US cohort. Both the BMI- and WC-protein signatures were strongly associated with cardiometabolic risk factors and the risk of type 2 diabetes and were enriched in pathways relating to cell signaling, systemic inflammation, and glucose and fat metabolism. Our protein signatures have potential uses for monitoring metabolically unhealthy obesity.","journal":"medRxiv","year":2023,"id":409836,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9415,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1015980,"name":"Bige Özkan","orcid":"0000-0003-2745-1189","position":1,"is_corresponding":false},{"id":986222,"name":"Yujian Liang","orcid":null,"position":2,"is_corresponding":false},{"id":1189712,"name":"Jiali Yao","orcid":"0000-0001-7269-4679","position":3,"is_corresponding":false},{"id":39523,"name":"Nang Ei Ei Khaing","orcid":"0000-0002-5361-0481","position":4,"is_corresponding":false},{"id":441182,"name":"Mary R. Rooney","orcid":"0000-0002-5607-4848","position":5,"is_corresponding":false},{"id":340495,"name":"Chiadi E. Ndumele","orcid":"0000-0002-1603-282X","position":6,"is_corresponding":false},{"id":1122,"name":"E. Shyong Tai","orcid":"0000-0003-2929-8966","position":7,"is_corresponding":false},{"id":23021,"name":"Josef Coresh","orcid":"0000-0002-4598-0669","position":8,"is_corresponding":false},{"id":240625,"name":"Xueling Sim","orcid":"0000-0002-1233-7642","position":9,"is_corresponding":false},{"id":260010,"name":"Rob M. van Dam","orcid":"0000-0002-7354-8734","position":10,"is_corresponding":false},{"id":1189711,"name":"Charlie G.Y. Lim","orcid":"0000-0002-6709-8722","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:21:31.144858Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}