Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors.

Epidemiological findings suggest a relationship between multiple sclerosis (MS) and cardiovascular disease (CVD) risk factors, although the nature of this relationship is not well understood.

We used genome-wide association study (GWAS) data to identify shared genetic factors (pleiotropy) between MS and CVD risk factors.

Using summary statistics from a large, recent GWAS (total n > 250,000 individuals), we investigated overlap in single nucleotide polymorphisms (SNPs) associated with MS and a number of CVD risk factors including triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index, waist-to-hip ratio, type 2 diabetes, systolic blood pressure, and C-reactive protein level.

Using conditional enrichment plots, we found 30-fold enrichment of MS SNPs for different levels of association with LDL and TG SNPs, with a corresponding reduction in conditional false discovery rate (FDR). We identified 133 pleiotropic loci outside the extended major histocompatibility complex with conditional FDR < 0.01, of which 65 are novel. These pleiotropic loci were located on 21 different chromosomes. Our findings point to overlapping pathobiology between clinically diagnosed MS and cardiovascular risk factors and identify novel common variants associated with increased MS risk.