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

Yang Zhang, Zhipeng Liu, Tasnim Choudhury, Marilyn C. Cornelis, Wanqing Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1761-1767
Number of pages7
JournalEuropean Journal of Nutrition
Issue number4
StatePublished - Jun 2021


  • Causal effect
  • Coffee
  • Genome-wide association study (GWAS)
  • Mendelian randomization
  • Nonalcoholic fatty liver disease (NAFLD)

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Medicine (miscellaneous)


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