Coffee is one of the most widely consumed stimulants worldwide and is generally considered to be safe or even beneficial for health. However, increased risk of myocardial infarction and hypertension has been suggested for individuals who carry a functional variant at cytochrome P450 1A2 (CYP1A2), which makes them less effective at metabolizing caffeine.
The aim of this study was to examine if the CYP1A2 genotype or a genetic score for caffeine metabolism (caffeine-GS) modifies the association between habitual coffee consumption and the risk of cardiovascular disease (CVD).
Genetic data and information on habitual coffee intake and relevant covariates were available for 347,077 individuals in the UK Biobank, including 8368 incident CVD cases. We used logistic regression to test for the association between coffee intake and CVD risk, and whether the association varies with CYP1A2 genotype or caffeine-GS.
The association between habitual coffee intake and CVD risk was nonlinear, and, compared with participants drinking 1-2 cups/day, the risk of CVD was elevated for nondrinkers, drinkers of decaffeinated coffee, and those who reported drinking >6 cups/day (increase in odds by 11%, 7%, and 22%, respectively, P-curvature = 0.013). CYP1A2 genotype and caffeine-GS were not associated with CVD (P = 0.22 for all comparisons). There was no evidence for an interaction between the CYP1A2 genotype or caffeine-GS and coffee intake with respect to risk of CVD (P = 0.53).
Heavy coffee consumption was associated with a modest increase in CVD risk, but this association was unaffected by genetic variants influencing caffeine metabolism.
Nutrition, diet and health: examining causal associations and gene-environment interactions
Using approaches from observational and genetic epidemiology, we propose to examine causal effects and gene-environment interactions affecting the way diet, obesity, or other nutritional factors affect health. The project has a specific focus on obesity and vitamin D, but it will also look at coffee, alcohol, and other components affecting nutritional intakes. Diet and nutritional status have a fundamental influence on health, and we will look at influences on aging, endocrinological, cardiovascular, metabolic and musculoskeletal health. This study will establish new disease prevention strategies, and inform on the way we can overcome disease inducing genetic vulnerabilities by lifestyle choices. This study will aim to establish new disease prevention strategies, and inform on the way we can overcome disease inducing genetic vulnerabilities by lifestyle choices. This study will use observational and genetic epidemiological approaches using existing information. We will conduct Mendelian randomisation (MR) analyses using genetic proxy markers for variations in nutritional exposures to evaluate the causal effects on the outcome. Analyses will be bi-directional where direction of association is not known, and network MR analyses will be conducted to establish causal pathways. Gene-environment interaction analyses will be conducted to establish effect modification by dietary and nutritional indicators in the way genes affect health. Full cohort
|Lead investigator:||Professor Elina Hypponen|
|Lead institution:||University of South Australia|
2 related Returns
|Return ID||App ID||Description||Archive Date|
|2758||20175||Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants||3 Nov 2020|
|2759||20175||Vitamin D and cognitive function: A Mendelian randomisation study||3 Nov 2020|
|2758||Long-term coffee consumption, caffeine metabolism genetics, and risk of cardiovascular disease: a prospective analysis of 347,077 individuals and 8368 cases||Zhou & Hypponen||2019||The American Journal of Clinical Nutrition (2019)|