Association Between Metabolically Different Adiposity Subtypes and Osteoarthritis: A Mendelian Randomization Study.
Anwar Mulugeta1, Tesfahun C Eshetie2, Gizat M Kassie3
1University of South Australia and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia, and Addis Ababa University, Addis Ababa, Ethiopia.
Arthritis Care & Research
|March 21, 2022
Summary
Metabolically unfavorable and neutral adiposity increase osteoarthritis risk. The link between adiposity and osteoarthritis may be mechanical, not metabolic.
Area of Science:
- Genetics
- Metabolic Health
- Osteoarthritis Research
Background:
- Adiposity is a known risk factor for osteoarthritis.
- The specific metabolic profiles of different adiposity subtypes and their causal impact on osteoarthritis remain unclear.
Purpose of the Study:
- To investigate the causal effect of metabolically distinct adiposity subtypes on osteoarthritis using Mendelian randomization (MR).
Main Methods:
- Two-sample MR analysis using summary-level data for osteoarthritis and site-specific osteoarthritis.
- Utilized genetic instruments associated with body mass index and varying metabolic profiles (unfavorable, neutral, favorable).
- Employed inverse variance weighting (IVW) for primary analysis and sensitivity analyses with nonlinear MR.
Main Results:
- Metabolically unfavorable and neutral adiposity were significantly associated with increased odds of osteoarthritis.
- All adiposity subtypes showed increased odds for knee osteoarthritis.
- Nonlinear MR indicated a nonlinear relationship between metabolically unfavorable adiposity and osteoarthritis.
Conclusions:
- Metabolic abnormalities do not fully explain the association between adiposity and osteoarthritis risk.
- The observed link between greater adiposity and osteoarthritis may primarily stem from mechanical effects on joints.
