TY - JOUR
T1 - Association Between Metabolically Different Adiposity Subtypes and Osteoarthritis
T2 - A Mendelian Randomization Study
AU - Mulugeta, Anwar
AU - Eshetie, Tesfahun C.
AU - Kassie, Gizat M.
AU - Erku, Daniel
AU - Mekonnen, Alemayehu
AU - Lumsden, Amanda
AU - Hyppönen, Elina
PY - 2023/4
Y1 - 2023/4
N2 - Objective: In this Mendelian randomization (MR) study, the objective was to investigate the causal effect of metabolically different adiposity subtypes on osteoarthritis. Methods: We performed 2-sample MR using summary-level data for osteoarthritis (10,083 cases and 40,425 controls) from a genome-wide association using the UK Biobank, and for site-specific osteoarthritis from the Arthritis Research UK Osteoarthritis Genetics consortium. We used 3 classes of genetic instruments, which all increase body mass index but are associated with different metabolic profiles (unfavorable, neutral, and favorable). Primary analysis was performed using inverse variance weight (IVW), with additional sensitivity analysis from different MR methods. We further applied a nonlinear MR using UK Biobank data to understand the nature of the adiposity–osteoarthritis relationship. Results: Greater metabolically unfavorable and metabolically neutral adiposity were associated with higher odds of osteoarthritis (IVW odds ratio [OR] 1.56 [95% confidence interval (95% CI) 1.31, 1.85] and OR 1.60 [95% CI 1.15, 2.23], respectively). The estimate for the association between metabolically favorable adiposity and osteoarthritis was similar, although with notable imprecision (OR 1.55 [95% CI 0.70, 3.41]). Using site-specific osteoarthritis, metabolically unfavorable, neutral, and favorable adiposity were all associated with higher odds of knee osteoarthritis (OR 1.44 [95% CI 1.04, 1.98], OR 2.28 [95% CI 1.04, 4.99], and OR 6.80 [95% CI 2.08, 22.19], respectively). We found generally consistent estimates with a wider confidence interval crossing the null from other MR methods. The nonlinear MR analyses suggested a nonlinear relationship between metabolically unfavorable adiposity and osteoarthritis (Pnonlinear = 0.003). Conclusion: Metabolic abnormalities did not explain the association between greater adiposity and the risk of osteoarthritis, which might suggest that the association is largely due to a mechanical effect on the joints.
AB - Objective: In this Mendelian randomization (MR) study, the objective was to investigate the causal effect of metabolically different adiposity subtypes on osteoarthritis. Methods: We performed 2-sample MR using summary-level data for osteoarthritis (10,083 cases and 40,425 controls) from a genome-wide association using the UK Biobank, and for site-specific osteoarthritis from the Arthritis Research UK Osteoarthritis Genetics consortium. We used 3 classes of genetic instruments, which all increase body mass index but are associated with different metabolic profiles (unfavorable, neutral, and favorable). Primary analysis was performed using inverse variance weight (IVW), with additional sensitivity analysis from different MR methods. We further applied a nonlinear MR using UK Biobank data to understand the nature of the adiposity–osteoarthritis relationship. Results: Greater metabolically unfavorable and metabolically neutral adiposity were associated with higher odds of osteoarthritis (IVW odds ratio [OR] 1.56 [95% confidence interval (95% CI) 1.31, 1.85] and OR 1.60 [95% CI 1.15, 2.23], respectively). The estimate for the association between metabolically favorable adiposity and osteoarthritis was similar, although with notable imprecision (OR 1.55 [95% CI 0.70, 3.41]). Using site-specific osteoarthritis, metabolically unfavorable, neutral, and favorable adiposity were all associated with higher odds of knee osteoarthritis (OR 1.44 [95% CI 1.04, 1.98], OR 2.28 [95% CI 1.04, 4.99], and OR 6.80 [95% CI 2.08, 22.19], respectively). We found generally consistent estimates with a wider confidence interval crossing the null from other MR methods. The nonlinear MR analyses suggested a nonlinear relationship between metabolically unfavorable adiposity and osteoarthritis (Pnonlinear = 0.003). Conclusion: Metabolic abnormalities did not explain the association between greater adiposity and the risk of osteoarthritis, which might suggest that the association is largely due to a mechanical effect on the joints.
KW - osteoarthritis
KW - Mendelian randomization study
UR - http://www.scopus.com/inward/record.url?scp=85143209678&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1157281
U2 - 10.1002/acr.24884
DO - 10.1002/acr.24884
M3 - Article
C2 - 35313082
AN - SCOPUS:85143209678
SN - 2151-464X
VL - 75
SP - 885
EP - 892
JO - Arthritis Care and Research
JF - Arthritis Care and Research
IS - 4
ER -