Abstract
We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the diseases was tested with multivariate analysis. Among the six modules significantly correlated with early traits of both the diseases, two had significant (adjusted p-values (p.adj) < 0.05) and another two had suggestively significant (p.adj < 0.25) joint association with the two diseases after adjusting for age, sex, body mass index, smoking habit, alcohol consumption, and physical activity. The three most significant member genes from the significant modules were NOSIP, GXYLT2, and TRIM63 (p.adj ≤ 0.18). Genes in the modules were enriched with biological processes that have separately been found to be involved in either bone metabolism or atherosclerosis. The gene modules and their most significant member genes identified in this study support the osteoporosis-atherosclerosis comorbidity hypothesis and can provide new joint biomarkers for both diseases and their dual prevention.
Highlights
ObjectivesThe objective of the present study was to perform a system-level analysis of genome-wide expression data in whole blood, used as a proxy for difficult-to-acquire samples such as bone or artery wall tissue, to identify gene co-expression modules, enriched pathways in the identified modules and the most important member genes jointly and significantly associated with the early traits of both osteoporosis and atherosclerosis
Believe that the results show a suggestive joint association between the modules and traits of the diseases that warrants further research in a case–control setting that includes participants with clinically diagnosed osteoporosis and atherosclerosis
There is a lack of omics-based studies investigating osteoporosis and atherosclerosis comorbidity in the literature despite strong and clear indications from several studies that the diseases are comorbid
Summary
The objective of the present study was to perform a system-level analysis of genome-wide expression data in whole blood, used as a proxy for difficult-to-acquire samples such as bone or artery wall tissue, to identify gene co-expression modules, enriched pathways in the identified modules and the most important member genes jointly and significantly associated with the early traits of both osteoporosis and atherosclerosis
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