@article{ef848f7e2a974cf28247d62eef8e6264,
title = "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",
abstract = "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.",
keywords = "Atherosclerosis, Co/multimorbidity, Gene set analysis, Osteoporosis, Transcriptomics",
author = "Mishra, {Binisha H.} and Harri Siev{\"a}nen and Emma Raitoharju and Nina Mononen and Jorma Viikari and Markus Juonala and Marika Laaksonen and Nina Hutri-K{\"a}h{\"o}nen and Mika K{\"a}h{\"o}nen and Raitakari, {Olli T.} and Terho Lehtim{\"a}ki and Mishra, {Pashupati P.}",
note = "Funding Information: The Young Finns Study has been financially supported by the Academy of Finland: grants 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), 41071 (Skidi), 330809 and 338395; the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Sigrid Jus{\'e}lius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrj{\"o} Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreements No 848146 (To Aition) and No 755320 (TAXINOMISIS); This project has received funding from the European Research Council (ERC) advanced grants under grant agreement No 742927 (MULTIEPIGEN project); Tampere University Hospital Supporting Foundation and Finnish Society of Clinical Chemistry. Binisha H. Mishra was supported by: Laboratoriol{\"a}{\"a}ketieteen Edist{\"a}miss{\"a}{\"a}ti{\"o} Sr; Ida Montinin S{\"a}{\"a}ti{\"o}; Kalle Kaiharin s{\"a}{\"a}ti{\"o}; the Finnish Cultural Foundation (grant 50191928); Aarne Koskelon s{\"a}{\"a}ti{\"o} and Faculty of Medicine and Health Technology, Tampere University. Pashupati P. Mishra was supported by the Academy of Finland (Grant number: 349708). Funding Information: The Young Finns Study has been financially supported by the Academy of Finland : grants 322098 , 286284 , 134309 (Eye), 126925 , 121584 , 124282 , 129378 (Salve), 117787 (Gendi), 41071 (Skidi), 330809 and 338395 ; the Social Insurance Institution of Finland ; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001 ); Juho Vainio Foundation ; Paavo Nurmi Foundation ; Finnish Foundation for Cardiovascular Research ; Finnish Cultural Foundation ; Sigrid Jus{\'e}lius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrj{\"o} Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreements No 848146 (To Aition) and No 755320 (TAXINOMISIS); This project has received funding from the European Research Council (ERC) advanced grants under grant agreement No 742927 (MULTIEPIGEN project); Tampere University Hospital Supporting Foundation and Finnish Society of Clinical Chemistry. Binisha H. Mishra was supported by: Laboratoriol{\"a}{\"a}ketieteen Edist{\"a}miss{\"a}{\"a}ti{\"o} Sr; Ida Montinin S{\"a}{\"a}ti{\"o}; Kalle Kaiharin s{\"a}{\"a}ti{\"o}; the Finnish Cultural Foundation (grant 50191928 ); Aarne Koskelon s{\"a}{\"a}ti{\"o} and Faculty of Medicine and Health Technology , Tampere University. Pashupati P. Mishra was supported by the Academy of Finland (Grant number: 349708 ). Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = nov,
doi = "10.1016/j.atherosclerosis.2022.10.005",
language = "English",
volume = "361",
pages = "1--9",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier",
}