Coffee and the risk of osteoarthritis: a two-sample, two-step multivariable Mendelian randomization study

Zhang W, Lei X, Tu Y, Ma T, Wen T, Yang T, Xue L, Ji J, Xue H · Frontiers in Genetics

Coffee intake was associated with higher OA risk across sites, largest for knee OA (OR 2.03, 95% CI 1.57-2.61, p < 0.001) and smallest for self-reported OA (OR 1.03, 1.01-1.05). Body mass index mediated more than half of the total effect; bone mineral density under 5%. By type, only **decaffeinated** coffee was causally associated with knee OA (OR 4.40, 95% CI 1.71-11.33) and with self-reported OA (1.13, 1.02-1.26).

Population

GWAS summary statistics for coffee intake and for knee, hip, knee-or-hip, total and self-reported osteoarthritis, with BMI and bone mineral density tested as mediators

Intervention

Genetically predicted coffee intake, including by coffee type

Comparator

Lower genetically predicted intake

Limitations

The decaffeinated finding is the tell: an odds ratio of 4.40 for decaf and nothing for ground or instant coffee is far more consistent with the instrument capturing who chooses decaf — older, more health-conscious, more likely to have been told to cut down — than with a biological effect of removing caffeine. That BMI mediates most of the total effect says the same thing in another way. European-ancestry GWAS.