Obesity-Related Genes Are Associated With an Increased Risk of Rheumatoid Arthritis

Higher body mass index (BMI) based on genes is associated with a risk of developing rheumatoid arthritis (RA), according to an analysis of genetic data published in Arthritis & Rheumatology.

The study utilized data from 850,000 individuals of European ancestry for 3 obesity-related traits: BMI, waist-to-hip ratio (WHR), and WHR adjusted for BMI (WHRadjBMI). Although RA is more prevalent in women than men, the association between obesity-related genes and RA risk was the same for men and women.

While environmental triggers can be difficult to pinpoint, Mendelian randomization (MR) uses genetic variants as instrumental variables and allows researchers to make casual inferences between exposures and outcomes.

“In addition to explore a causal relationship, we also quantified genetic correlation, a measure of shared genetic overlap, between obesity-related traits and RA,” the authors wrote.

They found that “obesity-related traits were strongly genetically correlated with each other” and there was a common genetic basis for BMI and WHR. However, WHRadjBMI removes the effect of BMI from WHR, and for that trait, there was minimal correlated with BMI.

“These results illustrate the challenge of studying obesity-related traits alone and without a genetic context, as their effects are difficult to dissect,” the authors explained.

They then used the MR analysis to explore causal relationships between different measures of obesity and RA. They found a 15% increase for risk of RA with BMI (98% power), WHR (86% power), and WHRadjBMI (96% power). The power was only slightly decreased in males compared with females:

• In females: 80% power to detect a 15% increase in BMI, 15% in WHR, and 10% in WHRadjBMI
• In males: 80% power to detect a 15% increase in BMI, 25% in WHR, and 25% in WHRadjBMI

There was a 20% increased risk of RA per SD increment in BMI. However, they did not find any association between genetically predicted WHR and RA. They determined there was a “causal role of BMI but not WHR in the development of RA.” As a result, they investigated WHRadjBMI and did not observe any increased effect of WHRadjBMI with RA.

“These results highlight an important role of obesity in the pathological development of rheumatoid arthritis, as well as provide a potential actionable preventive strategy,” senior author Xia Jiang, PhD, of the Karolinska Institute, in Sweden, said in a statement. “Future studies are needed to understand the biological mechanisms underlying such a link, and to understand how obesity may causally influence rheumatoid arthritis prognosis.”

Reference

Tang B, Shi H, Alfredsson L, Klareskog L, Padyukov L, Jiang X. Obesity‐related traits and the development of rheumatoid arthritis – evidence from genetic data. Arthritis Rheum. Published online September 22, 2020. doi:10.1002/art.41517