Characterizing causal relationships of visceral fat and body shape on multiple sclerosis risk.

Abstract

Epidemiologic studies have established obesity as a risk factor for multiple sclerosis (MS). These studies relied on body-mass index (BMI) and body size silhouettes as the primary measures of obesity. Unfortunately, the causal mechanisms through which obesity confers MS risk are not yet known. To investigate the causal effects of multiple specific measures of body fat on MS risk in populations of European descent, using Mendelian randomization (MR). MR is a genetic instrumental variable analysis utilizing genome-wide association (GWA) summary statistics to infer causality between phenotypes. MR analyses were performed to investigate the relationships between seven measures of body fat (BMI, waist-hip ratio, visceral adipose tissue [VAT], subcutaneous adipose tissue, and arm-, leg-, and trunk-fat to total body fat ratio) and MS risk. Only BMI and VAT were significantly associated with MS risk in separate MR analyses (βBMI=0.27, pBMI<0.001; βVAT=0.28, pVAT=0.006). High correlation between BMI and VAT instruments suggest that two-sample MR associations for BMI and VAT likely capture the same causal mechanisms. BMI and VAT were causally associated with MS risk in European populations, though their effects do not appear independent, suggesting overlap in the role of overall body mass and visceral obesity in MS pathogenesis.