Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Am J Kidney Dis. 2022 Jan;79(1):9-14.e1. doi: 10.1053/j.ajkd.2021.04.018. Epub 2021 Oct 21.
RATIONALE & OBJECTIVE: 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.
SETTING & PARTICIPANTS: 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.
观察性研究表明，咖啡和咖啡因的摄入与肾结石风险降低有关。我们进行了一项孟德尔随机化研究，以评估这些关联的因果性质。
孟德尔随机化分析。
从先前发表的荟萃分析中选择与咖啡和咖啡因摄入相关的全基因组显著水平的独立遗传变异作为工具变量。肾结石的汇总水平数据来自英国生物库研究（6536 例病例和 388508 例非病例）和芬兰人群遗传研究联合会（3856 例病例和 172757 例非病例）。
遗传预测的咖啡和咖啡因摄入。
临床诊断的肾结石。
使用孟德尔随机化方法计算因果估计值。来自两个来源的估计值使用固定效应荟萃分析方法进行合并。
遗传预测的咖啡和咖啡因摄入与英国生物库研究中的肾结石风险降低相关，且在芬兰人群遗传研究联合会中的关联方向相似。肾结石的合并比值比为 0.60（95%置信区间，0.46-0.79；P<0.001），每增加 50%的遗传预测咖啡摄入量和 0.81（95%置信区间，0.69-0.94；P=0.005）的遗传预测咖啡因摄入量，肾结石的风险降低。
遗传因素通过不涉及咖啡或咖啡因的途径对肾结石风险的影响。
使用遗传数据，本研究提供了证据表明，更高的咖啡和咖啡因摄入可能会降低肾结石的发生风险。
