Genetics

This post covers Yu and colleagues' 2024 Nutrition Journal study, which stacked four layers of evidence on vitamin D and MS: a prospective cohort of 413,594 UK Biobank participants with 861 incident cases, genetic correlation, shared loci, and bidirectional Mendelian randomization. It follows the selection chain behind the cohort, the L-shaped curve with its inflection point at 47.9 nmol/L and the sex divergence around it, the genetic correlation and the four loci with strong colocalization evidence at RREB1, SMARCA4 with LDLR, SCGN and CDK4, the three parallel gene-mapping routes and the lipid pathway enrichment they converge on, the MR result and the immune cell mediation estimate of 32 to 45 per cent, and the tension the authors name between a cohort that finds a threshold and an MR method that cannot test one.