Genetics

This blog post reviews Zhou et al. (2017), a prospective, longitudinal genome-wide association study designed to identify genetic variants that influence relapse risk in multiple sclerosis (MS), shifting the focus from disease susceptibility to post-onset clinical course. Using recurrent-event survival modelling across three independent cohorts (adult MS, post–first demyelinating event conversion, and paediatric MS), the study reports a genome-wide significant association between an intronic variant in LRP2 (rs12988804) and increased relapse hazard, with consistent direction of effect across cohorts. The post discusses the study’s design strengths—particularly neurologist-verified relapse ascertainment and time-to-event methods suited to repeated relapses—alongside biological plausibility for LRP2 in neurodevelopment and repair-related pathways, key limitations due to sample size, and the implications for building larger longitudinal consortia to validate and translate relapse-modifying genetics into clinically useful stratification tools.