Causal association of monounsaturated fatty acids with rheumatoid arthritis but not osteoarthritis: A two-sample Mendelian randomization study

Objectives: Previous studies have indicated that dietary monounsaturated fatty acids (MUFAs) are associated with decreased risk of osteoarthritis (OA) and rheumatoid arthritis (RA). However, the causality of the observed associations is largely undetermined. We sought to ascertain the potential causal roles of two of the most common MUFAs, oleic acid and palmitoleic acid, in RA and OA risk using a two-sample Mendelian randomization approach. Methods: For the outcomes, we used summary-level data for RA (14361 people with RA and 43 923 controls) and OA (10083 people with OA and 40425 controls) from two genome-wide association studies in European ancestry. For the exposures, five single-nucleotide polymorphisms associated with palmitoleic acid and one associated with oleic acid with genome-wide significance (P < 5 x 10(-8)) were selected as instrumental variables. The causal effects were estimated using the inverse-variance weighted method with several sensitivity analyses. Results: For genetically predicted levels, an increase of one SD in palmitoleic acid (odds ratio, 0.24; 95% confidence interval, 0.10-0.59; P = 0.002) and oleic acid (odds ratio, 0.78; 95% confidence interval, 0.67-0.90; P < 0.001) was significantly associated with lower risk of RA. However, genetic predisposition to either of the two individual MUFAs was not associated with OA risk. Sensitivity analyses yielded similar results. Conclusions: Our Mendelian randomization analyses suggest a causal relationship between higher genetically predicted MUFA levels and lower risks of RA. However, the causality between MUFAs and OA cannot be inferred from this study. Further research is required to unravel the role of MUFA supplementation in arthritis prevention. (C) 2021 Elsevier Inc. All rights reserved.