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

Gill, D; Karhunen, V; Malik, R; Dichgans, M; Sofat, N (2021) Cardiometabolic traits mediating the effect of education on osteoarthritis risk: a Mendelian randomization study. Osteoarthritis Cartilage, 29 (3). pp. 365-371. ISSN 1522-9653 https://doi.org/10.1016/j.joca.2020.12.015
SGUL Authors: Sofat, Nidhi Gill, Dipender Preet Singh

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Abstract

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.

Item Type: Article
Additional Information: © 2021 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Cardiometabolic, Education, Mendelian randomization, Osteoarthritis, 1103 Clinical Sciences, Arthritis & Rheumatology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Osteoarthritis Cartilage
ISSN: 1522-9653
Language: eng
Dates:
DateEvent
March 2021Published
7 January 2021Published Online
29 December 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
204809/Z/16/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
203928/Z/16/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
RE/18/4/34215British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
666881Horizon 2020UNSPECIFIED
667375Horizon 2020UNSPECIFIED
390857198Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659
Health-F2-2013-601456Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
PubMed ID: 33422704
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112776
Publisher's version: https://doi.org/10.1016/j.joca.2020.12.015

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