Coffee Types and Cardiac Metabolic Risks: Large-scale Cross-phenotype Association Study and Mendelian Randomization Analysis

Abstract

\n Purpose: To explore whether coffee intake is associated with cardiac metabolic risks from a genetic perspective, and whether this association remains the same among different types of coffee consumers.Methods: We utilised the summary-level results of 28 genome-wide association studies (total sample size: ~5,000,000). First, we used linkage disequilibrium score regression and cross-phenotypic association analysis to estimate the genetic correlation and identify shared genes between coffee intake and various cardiac metabolic risks. Second, we used Mendelian randomization (MR) analysis to test whether there was a significant genetically predicted causal association between coffee intake and cardiac metabolic risks. For all the analyses above, we also conducted a separate analysis for different types of coffee consumers, in addition to total coffee intake.Results: Genetically, coffee intake and choice for decaffeinated/instant coffee had significant positive correlation with body mass index (BMI) and some other cardiac metabolic risks, while choice for ground coffee was significantly negatively associated with these risks. Between these genetically related phenotypes, there were 1708 genomic shared regions, of which 139 loci were novel. Enrichment analysis showed that these shared genes were significantly enriched in antigen processing related biological processes. MR analysis indicated that higher genetically proxied coffee intake may increase BMI (b: 0.35, p-value: 1.80ⅹ10-05), while genetically proxied choice for ground coffee can reduce BMI (b: -0.08, p-value: 6.50ⅹ10-05), and the risk of T2D (T2D: b: -0.2, p-value: 4.70ⅹ10-10; T2D adjusted for BMI: b: -0.11, p-value: 4.60ⅹ10-05).Conclusions: Compared with other types of coffee, ground coffee has a significant negative genetic and genetically predicated causal relationship with cardiac metabolic risks. And this association is likely to be mediated by immunity. The effect of different coffee types on cardiac metabolic risks is not equal, researchers on coffee should pay more attention to distinguishing between coffee types.