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Associations of Blood Caffeine and Genetically Predicted Coffee Consumption with Anthropometric Measures of Obesity: A Two Sample Mendelian Randomization Study

  • Original Research
  • Published:
The journal of nutrition, health & aging

Abstract

Objectives

In observational studies, caffeine has been associated with a lower risk of obesity. However, whether the associations are causal and apply to coffee, which is a mixture of chemical compounds is unclear.

Design

Two sample Mendelian randomization study.

Setting and Participants

Genetic instruments predicting caffeine were extracted from an existing GWAS of serum metabolites in 1960 individuals of European descent. For coffee consumption up to 91,462 individuals of European ancestry with top SNPs followed-up in ∼30,062 coffee consumers and up to 375,833 individuals of European ancestry were taken from two separate studies. Genetic associations with obesity classes (n= 263,407), waist-to-hip ratio (WHR) (n=210,086), waist circumference (WC) (n= 231,355), and hip circumference (HC) (n=211,117) were obtained from summary statistics of individuals of European ancestry from the Genetic Investigation of Anthropocentric Traits (GIANT).

Methods

The inverse-variance weighted method (IVW) was used as the main analysis. We also employed the weighted median approach (WM) and MR-Egger regression as sensitivity analyses. To gauge evidence of directional pleiotropy, we used Cochrane’s Q test, and MR-PRESSO global test, as measures of heterogeneity between ratio estimates of variants.

Results

There was little evidence to support an association between blood caffeine and any anthropometric measure of obesity in the primary and sensitivity analyses. However, genetically predicted coffee consumption was positively associated with higher class I obesity and WHR. Furthermore, this association was maintained after correction for multiple testing (P < 0.05/6 = 0.008). Results from the GWAS of coffee consumption were in tandem with results from the GWMA, but associations with class I obesity and waist to hip ratio (WHR) were not maintained after correction for multiple testing.

Conclusion

We found little evidence that caffeine or coffee consumption protects against obesity, adding to growing literature suggesting that previous observational studies may have been confounded. This study demonstrates the dangers of ignoring genetic testing for targeted interventions and basing dietary policy recommendations solely on observational studies restricted to specific populations.

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Abbreviations

GWMA:

genome wide meta-analysis

GWAS:

genome wide association study

MR:

mendelian randomization

IVs:

instrument variables

SNP:

single nucleotide polymorphism

IVW:

Inverse weighted median

WM:

weighted median

ME:

MR-Egger

WHO:

World Health Organization

BMI:

Body Mass Index

WC:

waist circumference

HC:

hip circumference

WHR:

waist to hip ratio

GIANT:

Genetic Investigation of Anthropocentric Traits

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Authors and Affiliations

  1. The School of Biological Sciences, The University of Queensland, St. Lucia, Qld, 4072, Australia

    Vikram P. Narayan

  2. College of Life and Environmental Sciences, University of Exeter, Penryn, UK

    Vikram P. Narayan

  3. System Health & Engineering Major in Graduate School (BK21 Plus Program), Ewha Womans University, Seoul, 03760, Korea

    S. Y. Yoon

  4. Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 03760, Korea

    S. Y. Yoon

Authors
  1. Vikram P. Narayan
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Contributions

V.P.N conducted data analysis and drafted the manuscript. V.P.N and S.Y. Y interpreted findings and critically reviewed the manuscript.

Corresponding author

Correspondence to Vikram P. Narayan.

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Conflict of Interest Statement

The authors declare no conflict of interest.

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Narayan, V.P., Yoon, S.Y. Associations of Blood Caffeine and Genetically Predicted Coffee Consumption with Anthropometric Measures of Obesity: A Two Sample Mendelian Randomization Study. J Nutr Health Aging 26, 190–196 (2022). https://doi.org/10.1007/s12603-022-1736-5

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  • DOI: https://doi.org/10.1007/s12603-022-1736-5

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