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Cardiometabolic traits mediating the effect of education on osteoarthritis risk: a Mendelian randomization study

OBJECTIVE: To investigate which cardiometabolic factors underlie clustering of osteoarthritis (OA) with cardiovascular disease, and the extent to which these mediate an effect of education. DESIGN: Genome-wide association study (GWAS) of OA was performed in UK Biobank (60,800 cases and 328,251 contr...

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Autores principales: Gill, D., Karhunen, V., Malik, R., Dichgans, M., Sofat, N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: W.B. Saunders For The Osteoarthritis Research Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955282/
https://www.ncbi.nlm.nih.gov/pubmed/33422704
http://dx.doi.org/10.1016/j.joca.2020.12.015
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author Gill, D.
Karhunen, V.
Malik, R.
Dichgans, M.
Sofat, N.
author_facet Gill, D.
Karhunen, V.
Malik, R.
Dichgans, M.
Sofat, N.
author_sort Gill, D.
collection PubMed
description OBJECTIVE: To investigate which cardiometabolic factors underlie clustering of osteoarthritis (OA) with cardiovascular disease, and the extent to which these mediate an effect of education. DESIGN: Genome-wide association study (GWAS) of OA was performed in UK Biobank (60,800 cases and 328,251 controls) to obtain genetic association estimates for OA risk. Genetic instruments and association estimates for body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), smoking and education were obtained from existing GWAS summary data (sample sizes 188,577–866,834 individuals). Two-sample Mendelian randomization (MR) analyses were performed to investigate the effects of exposure traits on OA risk. MR mediation analyses were undertaken to investigate whether the cardiometabolic traits mediate any effect of education on OA risk. RESULTS: MR analyses identified protective effects of higher genetically predicted education (main MR analysis odds ratio (OR) per standard deviation increase 0.59, 95% confidence interval (CI) 0.54–0.64) and LDL-C levels (OR 0.94, 95%CI 0.91–0.98) on OA risk, and unfavourable effects of higher genetically predicted BMI (OR 1.82, 95%CI 1.73–1.92) and smoking (OR 2.23, 95%CI 1.85–2.68). There was no strong evidence of an effect of genetically predicted SBP on OA risk (OR 0.98, 95% CI 0.90–1.06). The proportion of the effect of genetically predicted education mediated through genetically predicted BMI and smoking was 35% (95%CI 13–57%). CONCLUSIONS: These findings highlight education, obesity and smoking as common mechanisms underlying OA and cardiovascular disease. These risk factors represent clinical and public health targets for reducing multi-morbidity related to the burden these common conditions.
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spelling pubmed-79552822021-03-18 Cardiometabolic traits mediating the effect of education on osteoarthritis risk: a Mendelian randomization study Gill, D. Karhunen, V. Malik, R. Dichgans, M. Sofat, N. Osteoarthritis Cartilage Article OBJECTIVE: To investigate which cardiometabolic factors underlie clustering of osteoarthritis (OA) with cardiovascular disease, and the extent to which these mediate an effect of education. DESIGN: Genome-wide association study (GWAS) of OA was performed in UK Biobank (60,800 cases and 328,251 controls) to obtain genetic association estimates for OA risk. Genetic instruments and association estimates for body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), smoking and education were obtained from existing GWAS summary data (sample sizes 188,577–866,834 individuals). Two-sample Mendelian randomization (MR) analyses were performed to investigate the effects of exposure traits on OA risk. MR mediation analyses were undertaken to investigate whether the cardiometabolic traits mediate any effect of education on OA risk. RESULTS: MR analyses identified protective effects of higher genetically predicted education (main MR analysis odds ratio (OR) per standard deviation increase 0.59, 95% confidence interval (CI) 0.54–0.64) and LDL-C levels (OR 0.94, 95%CI 0.91–0.98) on OA risk, and unfavourable effects of higher genetically predicted BMI (OR 1.82, 95%CI 1.73–1.92) and smoking (OR 2.23, 95%CI 1.85–2.68). There was no strong evidence of an effect of genetically predicted SBP on OA risk (OR 0.98, 95% CI 0.90–1.06). The proportion of the effect of genetically predicted education mediated through genetically predicted BMI and smoking was 35% (95%CI 13–57%). CONCLUSIONS: These findings highlight education, obesity and smoking as common mechanisms underlying OA and cardiovascular disease. These risk factors represent clinical and public health targets for reducing multi-morbidity related to the burden these common conditions. W.B. Saunders For The Osteoarthritis Research Society 2021-03 /pmc/articles/PMC7955282/ /pubmed/33422704 http://dx.doi.org/10.1016/j.joca.2020.12.015 Text en © 2021 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gill, D.
Karhunen, V.
Malik, R.
Dichgans, M.
Sofat, N.
Cardiometabolic traits mediating the effect of education on osteoarthritis risk: a Mendelian randomization study
title Cardiometabolic traits mediating the effect of education on osteoarthritis risk: a Mendelian randomization study
title_full Cardiometabolic traits mediating the effect of education on osteoarthritis risk: a Mendelian randomization study
title_fullStr Cardiometabolic traits mediating the effect of education on osteoarthritis risk: a Mendelian randomization study
title_full_unstemmed Cardiometabolic traits mediating the effect of education on osteoarthritis risk: a Mendelian randomization study
title_short Cardiometabolic traits mediating the effect of education on osteoarthritis risk: a Mendelian randomization study
title_sort cardiometabolic traits mediating the effect of education on osteoarthritis risk: a mendelian randomization study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955282/
https://www.ncbi.nlm.nih.gov/pubmed/33422704
http://dx.doi.org/10.1016/j.joca.2020.12.015
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