Journal
ATHEROSCLEROSIS
Volume 361, Issue -, Pages 1-9Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2022.10.005
Keywords
Osteoporosis; Atherosclerosis; Co; multimorbidity; Transcriptomics; Gene set analysis
Funding
- Academy of Finland [349708, 322098, 286284, 134309, 126925, 121584, 124282, 129378, 117787, 41071, 330809, 338395]
- Social Insurance Institution of Finland
- Competitive State Research Financing of the Expert Responsibility area of Kuopio University Hospital [X51001]
- Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital [X51001]
- Competitive State Research Financing of the Expert Responsibility area of Turku University Hospital [X51001]
- Juho Vainio Foundation
- Paavo Nurmi Foundation
- Finnish Foundation for Cardiovascular Research
- Finnish Cultural Foundation
- Sigrid Juselius Foundation
- Tampere Tuberculosis Foundation
- Emil Aaltonen Foundation
- Yrjo Jahnsson Foundation
- Signe and Ane Gyllenberg Foundation
- Diabetes Research Foundation of Finnish Diabetes Association
- European Union's Horizon 2020 research and innovation programme [848146, 755320]
- European Research Council (ERC) [742927]
- Tampere University Hospital Supporting Foundation
- Finnish Society of Clinical Chemistry
- Laboratoriolaaketieteen Edistamissa atio Sr
- Ida Montinin Saatio
- Kalle Kaiharin saatio
- Finnish Cultural Foundation [50191928]
- Aarne Koskelonsaatio
- Faculty of Medicine and Health Technology, Tampere University
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This study aimed to identify the shared biological processes underlying atherosclerosis-osteoporosis co/multimorbidity. Gene set analysis was performed on whole-blood transcriptomic data, and novel biological processes associated with high carotid intima-media thickness (CIMT) were identified. However, no associations were found with reduced bone mineral density (BMD).
Aim: We aimed at identifying the shared biological processes underlying atherosclerosis-osteoporosis co/ multimorbidity. Methods: We performed gene set analysis (GSA) of whole-blood transcriptomic data to identify biological pro-cesses shared by the early markers of these two diseases. Early markers of diseases, carotid intima-media thickness (CIMT) for atherosclerosis and trabecular bone mineral density (BMD) from distal radius and tibia for osteoporosis, were used to categorize the study participants into cases and controls. Participants with high CIMT (>90th percentile) were defined as cases for subclinical atherosclerosis. Study population-based T-scores for BMD were calculated and T-score <=-1 was used for the definition of low BMD cases i.e., early indicator of osteoporosis.Results: We did not identify any gene sets jointly associated with early markers of atherosclerosis and osteopo-rosis. We identified three novel and replicated 234 gene sets significantly associated with high CIMT with false discovery rate (FDR) <= 0.01. Only two genes, both related to the immune system, were identified to be associated with high CIMT by traditional differential gene expression analysis. However, none of the studied gene sets or individual genes were significantly associated with tibial or radial BMD. The three novel CIMT associated gene sets contained genes involved in copper homeostasis, neural crest cell migration and nicotinate and nicotinamide metabolism. The 234 replicated gene sets in this study are related to the immune system, hypoxia and apoptosis, consistent with the existing literature on atherosclerosis.Conclusions: This study identified novel biological processes associated with high CIMT but not with reduced BMD.
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