Certain Obesity Features Tied to Multiple Sclerosis Genetic Risk

Body mass index (BMI) and the amount of visceral adipose tissue (VAT) may have a pleiotropic effect on the genetic risk for multiple sclerosis (MS), according to study results presented at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) held October 25-28, 2021 in Orlando, Florida.

Life-long obesity has been linked with MS risk in observational studies, however it remains unclear how this proinflammatory health state may increase the risk for MS.

To better assess the obesity-MS causal relationship, researchers from Case Western Reserve University performed a 2-sample Mendelian randomization study using data of BMI (n=681,275), waist-hip ratio (n=694,649), VAT (n=325,123), and segmental bioelectric impedance measurements of the ratio of total body fat to arm, leg, and trunk fat (n=362,499). MS genetic risk was determined from 14,802 cases and 27,703 controls.

Significant associations were observed between MS genetic risk and BMI (b, 0.25; P <.001) and VAT (b, 0.24; P =.04). These relationships remained significant after adjusting for horizontal pleiotropy (BMI: b, 0.25; P <.001; VAT: b, 0.35; P <.001). In addition, in the horizontal pleiotropy analysis, the ratio of leg fat to total body fat was observed to have a significant inverse association with MS (b, -0.27; P =.04).

These findings were formulated using data collected from the general population and should be confirmed among a population of patients with MS.

These data confirmed previously published data which linked obesity with MS. This study more precisely interrogated differing features of obesity, as there is large variation across body types, and not all obesity is equivalent. In this Mendelian randomization assessment, genetic risk for MS was found to have a pleiotropic link with BMI, VAT, and the ratio of leg fat to total body fat but was not found to be associated with waist-hip, arm fat to total body fat, or trunk fat to total fat ratios.

“Future work will investigate potential horizontal pleiotropic effects across the different measures of obesity, and the role such variants play in risk of MS,” the researchers concluded.

Reference

Misicka E and Briggs FBS. Higher Visceral Fat and Body Mass Index Increase Risk for Multiple Sclerosis. Presented at: CMSC 2021 Annual Meeting; October 25-28, 2021; Orlando, Florida. Whitaker Research Track.