Self-reported and genetically predicted coffee consumption and smoking in dementia: A Mendelian randomization study.

BACKGROUND AND AIMS: Studies of self-reported coffee consumption and smoking on risk of dementia have shown results conflicting with two-sample Mendelian randomization studies. We tested the hypotheses that coffee consumption and smoking influence risk of dementia using observational and one-sample Mendelian randomization designs with individual level data. METHODS: We included 114,551 individuals from two Danish general population cohorts (median age 58 years). First, we tested whether high self-reported coffee consumption/smoking were associated with risk of dementia. Second, whether genetically predicted high coffee consumption/smoking due to variation near CYP1A1/AHR/CHRNA3 genes were associated with risk of dementia. RESULTS: We observed 3,784 dementia events. Moderate self-reported coffee consumption was associated with low risk of all dementia and non-Alzheimer's dementia, with a similar trend for Alzheimer's disease. Genetically predicted high coffee consumption was associated with high risk of all dementia (hazard ratio [95% confidence interval] per +1 cup/day: 1.20 [1.01-1.42]), with a similar trend for non-Alzheimer's dementia (1.23 [0.95-1.53]). High self-reported smoking was associated with high risk of non-Alzheimer's dementia. High genetically predicted smoking was associated with a trend towards high risk of all dementia and Alzheimer's disease (hazard ratios per +1 pack-year: 1.04 [0.96-1.11]) and 1.06 [0.97-1.16]). CONCLUSIONS: Moderate self-reported coffee consumption was associated with low risk of all and non-Alzheimer's dementia, while high genetically predicted coffee consumption was associated with a trend towards the opposite. High self-reported smoking was associated with high risk of non-Alzheimer's dementia, with a similar trend for genetically predicted smoking on all dementia and Alzheimer's disease.

Causal relationship from coffee consumption to diseases and mortality: a review of observational and Mendelian randomization studies including cardiometabolic diseases, cancer, gallstones and other diseases.

PURPOSE: High coffee consumption is associated with low risk of mortality and morbidity, but the causality remains unclear. This review aims to discuss findings from observational studies on coffee consumption in context of Mendelian randomization studies. METHODS: The PubMed database was searched for all Mendelian randomization studies on coffee consumption and corresponding observational studies. RESULTS: High coffee consumption is associated with low risk of all-cause and cardiovascular mortality in observational studies (HRs of 0.85-0.90 vs. no/low consumers), with no support of causality in Mendelian randomization studies. Moderate/high consumption is associated with low risk of cardiometabolic diseases, including ischemic heart disease (HRs of 0.85-0.90 vs. no/low consumption), stroke (HRs of approximately 0.80 vs. no/low consumption), type 2 diabetes (HRs of approximately 0.70 vs. no/low consumption) and obesity in observational studies, but not in Mendelian randomization studies. High consumption is associated with low risk of endometrial cancer and melanoma and high risk of lung cancer in observational studies, but with high risk of colorectal cancer in Mendelian randomization studies. In observational and Mendelian randomization studies, high coffee consumption is associated with low risk of gallstones (HRs of 0.55-0.70 for high vs. no/low self-reported and 0.81 (0.69-0.96) for highest vs. lowest genetic consumption). CONCLUSION: High coffee consumption is associated with low risk of mortality, cardiometabolic diseases, some cancers and gallstones in observational studies, with no evidence to support causality from Mendelian randomization studies for most diseases except gallstones.