Genetically predicted circulating homocysteine, vitamin B12, and folate levels and risk of multiple sclerosis: evidence from a two-sample Mendelian randomization analysis

Mult Scler Relat Disord. 2021 Nov:56:103255. doi: 10.1016/j.msard.2021.103255. Epub 2021 Sep 5.

Abstract

The association between homocysteine and risk of multiple sclerosis (MS) remains unclear. We implemented a two-sample Mendelian randomization (MR) analysis to comprehensively investigate the causal relationships between circulating homocysteine, vitamin B12 (VitB12), and folate levels and MS with data from large-scale genome-wide association studies. MR results demonstrated an inverse association between genetically predicted higher circulating homocysteine levels (per 1 standard deviation (SD) increase) and risk of MS (OR 0.78, 95% CI 0.64-0.94, p = 0.0106). No significant causal relationships between genetically determined higher VitB12 and folate levels and MS were observed. Further studies are warranted to elucidate the potential mechanisms.

Keywords: Causality; Folate; Homocysteine; Mendelian randomization analysis; Multiple sclerosis; Vitamin B12.

Publication types

  • Letter

MeSH terms

  • Folic Acid
  • Genome-Wide Association Study
  • Homocysteine
  • Humans
  • Mendelian Randomization Analysis*
  • Multiple Sclerosis* / epidemiology
  • Multiple Sclerosis* / genetics
  • Vitamin B 12

Substances

  • Homocysteine
  • Folic Acid
  • Vitamin B 12