Genetics

his post covers Nataf and colleagues' 2024 study in the International Journal of Molecular Sciences, which redoes the gene prioritization for rs10191329, the only SNP associated with MS severity, and reaches the opposite conclusion to the original report. It follows what gene prioritization weighs and why proximity to a transcription start site is a weak discriminator, the Open Targets Genetics survey of 60 eQTL datasets showing no CNS association across 18 regions while NAGK carries the largest effect size in blood and in interferon-gamma-stimulated monocytes, the single-cell expression data placing NAGK in classical monocytes and dendritic cells rather than neural cells, the glycolytic protein network and the muramyl dipeptide-NOD2 trigger, the UDP-GlcNAc salvage pathway and glycosylation of MS-relevant immune molecules, and the three published-data objections the authors raise against the cognitive reserve reading.