Coffee and Caffeine Consumption and Risk of Kidney Stones: A Mendelian Randomization Study

Rationale & ObjectiveCoffee and caffeine consumption have been associated with a lower risk of kidney stones in observational studies. We conducted a Mendelian randomization study to assess the causal nature of these associations.Study DesignMendelian randomization analysis.Setting & ParticipantsIndependent genetic variants associated with coffee and caffeine consumption at the genome-wide significance level were selected from previously published meta-analyses as instrumental variables. Summary-level data for kidney stones were obtained from the UK Biobank study (6,536 cases and 388,508 noncases) and the FinnGen consortium (3,856 cases and 172,757 noncases).ExposureGenetically predicted coffee and caffeine consumption.OutcomeClinically diagnosed kidney stones.Analytical ApproachMendelian randomization methods were used to calculate causal estimates. Estimates from the 2 sources were combined using the fixed-effects meta-analysis methods.ResultsGenetically predicted coffee and caffeine consumption was associated with a lower risk of kidney stones in the UK Biobank study, and the associations were directionally similar in the FinnGen consortium. The combined odds ratio of kidney stones was 0.60 (95% CI, 0.46-0.79; P < 0.001) per a genetically predicted 50% increase in coffee consumption and 0.81 (95% CI, 0.69-0.94; P = 0.005) per a genetically predicted 80-mg increase in caffeine consumption.LimitationsGenetic influence on kidney stone risk via pathways not involving coffee or caffeine.ConclusionsUsing genetic data, this study provides evidence that higher coffee and caffeine consumption may cause a reduction in kidney stones. Coffee and caffeine consumption have been associated with a lower risk of kidney stones in observational studies. We conducted a Mendelian randomization study to assess the causal nature of these associations. Mendelian randomization analysis. Independent genetic variants associated with coffee and caffeine consumption at the genome-wide significance level were selected from previously published meta-analyses as instrumental variables. Summary-level data for kidney stones were obtained from the UK Biobank study (6,536 cases and 388,508 noncases) and the FinnGen consortium (3,856 cases and 172,757 noncases). Genetically predicted coffee and caffeine consumption. Clinically diagnosed kidney stones. Mendelian randomization methods were used to calculate causal estimates. Estimates from the 2 sources were combined using the fixed-effects meta-analysis methods. Genetically predicted coffee and caffeine consumption was associated with a lower risk of kidney stones in the UK Biobank study, and the associations were directionally similar in the FinnGen consortium. The combined odds ratio of kidney stones was 0.60 (95% CI, 0.46-0.79; P < 0.001) per a genetically predicted 50% increase in coffee consumption and 0.81 (95% CI, 0.69-0.94; P = 0.005) per a genetically predicted 80-mg increase in caffeine consumption. Genetic influence on kidney stone risk via pathways not involving coffee or caffeine. Using genetic data, this study provides evidence that higher coffee and caffeine consumption may cause a reduction in kidney stones.