Habitual coffee intake and risk for nonalcoholic fatty liver disease: a two-sample Mendelian randomization study.

COFFEE; CONFIDENCE intervals; FATTY liver; INGESTION; GENETIC polymorphisms; GENOMES; ODDS ratio; DISEASE risk factors

Purpose: Epidemiological studies support a protective role of habitual coffee and caffeine consumption against the risk of non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the causal relationship between coffee intake and the risk of NAFLD. Methods: We performed a two-sample Mendelian randomization (MR) analysis using SNPs associated with habitual coffee intake in a published genome-wide association study (GWAS) as genetic instruments and summary-level data from a published GWAS of NAFLD (1122 cases and 399,900 healthy controls) in the UK Biobank. The causal relationship was estimated with the inverse weighted method using a 4-SNP and 6-SNP instrument based on the single largest non-UK Biobank GWAS (n = 91,462) and meta-analysis (n = 121,524) of GWAS data on habitual coffee intake, respectively. To maximize power, we also used up to 77 SNPs associated with coffee intake at a liberal significance level (p ≤ 1e-4) as instruments. Results: We observed a non-significant trend towards a causal protective effect of coffee intake on NAFLD based upon either the 4-SNP (OR: 0.76; 95% CI 0.51, 1.14, p = 0.19) or 6-SNP genetic instruments (OR: 0.77; 95% CI 0.48, 1.25, p = 0.29). The result also remains non-significant when using the more liberal 77-SNP instrument. Conclusion: Our findings do not support a causal relationship between coffee intake and NAFLD risk. However, despite the largest-to-date sample size, the power of this study may be limited by the non-specificity and moderate effect size of the genetic alleles on coffee intake. [ABSTRACT FROM AUTHOR]

Copyright of European Journal of Nutrition is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)