Gene set analysis of transcriptomics data identifies new biological processes associated with early markers of atherosclerosis but not with those of osteoporosis: Atherosclerosis-osteoporosis co/multimorbidity study in the Young Finns Study.

Autor: Mishra BH; Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland. Electronic address: binisha.hamalmishra@tuni.fi., Sievänen H; The UKK Institute for Health Promotion Research, Tampere, Finland., Raitoharju E; Molecular Epidemiology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Tampere University Hospital, Tampere, Finland., Mononen N; Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland., Viikari J; Department of Medicine, University of Turku, Turku, Finland; Division of Medicine, Turku University Hospital, Turku, Finland., Juonala M; Department of Medicine, University of Turku, Turku, Finland; Division of Medicine, Turku University Hospital, Turku, Finland., Laaksonen M; Fazer Lab Research, Oy Karl Fazer Ab, Helsinki, Finland., Hutri-Kähönen N; Department of Paediatrics, Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Kähönen M; Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland., Raitakari OT; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland; Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland., Lehtimäki T; Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland., Mishra PP; Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
Jazyk: angličtina
Zdroj: Atherosclerosis [Atherosclerosis] 2022 Nov; Vol. 361, pp. 1-9. Date of Electronic Publication: 2022 Oct 08.
DOI: 10.1016/j.atherosclerosis.2022.10.005
Abstrakt: 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 processes 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 osteoporosis. 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.
Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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