Genetics

This blog post synthesizes Jacobs et al. (2021), which leverages UK Biobank-scale data to investigate whether genetic liability modifies the impact of established environmental risk factors for multiple sclerosis (MS). Using polygenic risk scores constructed with and without the MHC region and multivariable regression models of key exposures—including childhood obesity, smoking, and reproductive timing—the study provides evidence of additive interaction between childhood obesity and polygenic susceptibility. The analysis suggests that early-life adiposity may exert disproportionately greater effects among individuals with higher inherited risk, supporting an immunometabolic “synergy” model of MS pathogenesis and motivating both replication in independent cohorts and prevention strategies focused on modifiable exposures across the life course.