Associations of Homocysteine, Folate, and Vitamin B12 with Osteoarthritis: A Mendelian Randomization Study

Hong H, et al. · Nutrients

Genetically higher homocysteine modestly increased overall OA risk (OR 1.10, 95% CI 1.044-1.155) and hip OA (OR 1.17); knee OA was borderline (OR 1.08, 95% CI 1.000-1.167). Genetically higher folate appeared protective for overall OA (OR 0.87, 95% CI 0.783-0.961) but not for knee OA. Indirect support for the methylation pathway betaine acts on, not evidence for betaine itself.

Population

Large-scale human GWAS datasets (Mendelian randomization; site- and sex-specific OA)

Intervention

Genetically predicted homocysteine, folate and B12 levels; no supplement given

Comparator

Genetically lower homocysteine / higher folate

Limitations

Two-sample Mendelian randomization on GWAS summary data; effect sizes small; does not test betaine supplementation; pleiotropy possible.