Integrated proteomic and metabolomic modules identified as biomarkers of mortality in the Atherosclerosis Risk in Communities study and the African American Study of Kidney Disease and Hypertension.

Autor: Zhou L; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument St., Baltimore, MD, 21287, USA., Surapaneni A; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument St., Baltimore, MD, 21287, USA., Rhee EP; Nephrology Division and Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA., Yu B; Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA., Boerwinkle E; Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA., Coresh J; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument St., Baltimore, MD, 21287, USA., Grams ME; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument St., Baltimore, MD, 21287, USA.; Division of Precision Medicine, Department of Medicine, New York University, New York, NY, USA., Schlosser P; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument St., Baltimore, MD, 21287, USA. pschlos3@jhu.edu.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2022 Nov 03; Vol. 16 (1), pp. 53. Date of Electronic Publication: 2022 Nov 03.
DOI: 10.1186/s40246-022-00425-9
Abstrakt: Background: Proteins and metabolites are essential for many biological functions and often linked through enzymatic or transport reactions. Individual molecules have been associated with all-cause mortality. Many of these are correlated and might jointly represent pathways or endophenotypes involved in diseases.
Results: We present an integrated analysis of proteomics and metabolomics via a local dimensionality reduction clustering method. We identified 224 modules of correlated proteins and metabolites in the Atherosclerosis Risk in Communities (ARIC) study, a general population cohort of older adults (N = 4046, mean age 75.7, mean eGFR 65). Many of the modules displayed strong cross-sectional associations with demographic and clinical characteristics. In comprehensively adjusted analyses, including fasting plasma glucose, history of cardiovascular disease, systolic blood pressure and kidney function among others, 60 modules were associated with mortality. We transferred the network structure to the African American Study of Kidney Disease and Hypertension (AASK) (N = 694, mean age 54.5, mean mGFR 46) and identified mortality associated modules relevant in this disease specific cohort. The four mortality modules relevant in both the general population and CKD were all a combination of proteins and metabolites and were related to diabetes / insulin secretion, cardiovascular disease and kidney function. Key components of these modules included N-terminal (NT)-pro hormone BNP (NT-proBNP), Sushi, Von Willebrand Factor Type A, EGF And Pentraxin (SVEP1), and several kallikrein proteases.
Conclusion: Through integrated biomarkers of the proteome and metabolome we identified functions of (patho-) physiologic importance related to diabetes, cardiovascular disease and kidney function.
(© 2022. The Author(s).)
Databáze: MEDLINE
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