Genetic and Causal Relationship Between Coffee Intake and Cardiometabolic Risks: Cross-Phenotype Association And Mendelian Randomization Analysis

Abstract

Background: Many epidemiological studies have shown that there is a significant association between coffee intake and cardiometabolic diseases, which may be due to the common genetic structure or causal relationship. Methods: We used linkage disequilibrium score regression analysis to calculate the genetic correlation between coffee intake and 23 cardiometabolic traits (diseases), and then used cross-phenotype association analysis to identify the shared genetic loci for the trait pairs with significant genetic correlation. Besides, a bi-directional Mendelian Randomization analysis was used to explore the causal relationship between coffee intake and 23 cardiometabolic traits (diseases).Results: Coffee intake has a significant genetic correlation (after Bonferroni correction) with body mass index (BMI) (Rg = 0.3713, P-value = 4.13ⅹ10-64), body fat percentage (BF%) (Rg = 0.2810, P-value = 1.81ⅹ10-13), type 2 diabetes (T2D) (unadjusted for BMI) (Rg = 0.1189, P-value = 8.80ⅹ10-6), heart failure (HF) (Rg = 0.2626, P-value = 6.00ⅹ10-9), atrial fibrillation (AF) (Rg = 0.1007, P-value = 4.30ⅹ10-5). There are 203, 18, 86, 13, 38 independent shared loci between coffee intake and BMI, BF%, T2D, HF, AF, respectively, among which 22, 2, 23, 4,13 loci do not achieve genome-wide significance in single trait GWAS. Coffee intake has significant causal effect on BMI (b = 0.0717, P-value = 2.33ⅹ10-5), T2D (unadjusted for BMI, OR = 1.27, P-value = 1.46ⅹ10-7), and intracerebral haemorrhage (ICH) (all types ICH: OR = 1.86, P-value = 3.37ⅹ10-4; deep ICH: OR = 2.12, P-value = 2.93ⅹ10-4 ). And BMI (b = 0.3694, P-value=3.64ⅹ10-154), BF% (b = 0.5500, P-value = 1.68ⅹ10-4), T2D (adjusted for BMI, b = -0.0252, P-value = 4.83ⅹ10-6) and triglycerides (TG) (b = -0.1209, P-value = 4.56ⅹ10-15) have significant causal effect on coffee intake.Conclusions: Our study identified the shared genetic structure and causal relationship between coffee intake and several cardiometabolic traits (diseases), providing a new insight into the mechanism of coffee intake and cardiometabolic traits (diseases).