Coffee intake and risk of obesity, metabolic syndrome and type 2 diabetes: a Mendelian randomization study
Abstract
BACKGROUND: Coffee is one of the most widely consumed beverages. We tested the hypothesis that genetically high coffee intake is associated with low risk of obesity, metabolic syndrome and type 2 diabetes, and with related components thereof. METHODS: We included 93,179 individuals from two large general population cohorts in a Mendelian randomization study. We tested first whether high coffee intake is associated with low risk of obesity, metabolic syndrome and type 2 diabetes, and with related components thereof, in observational analyses; second, whether five genetic variants near the CYP1A1, CYP1A2 and AHR genes are associated with coffee intake; and third, whether the genetic variants are associated with obesity, metabolic syndrome and type 2 diabetes, and with related components thereof. Finally, we tested the genetic association with type 2 diabetes in a meta-analysis including up to 78,021 additional individuals from the DIAGRAM consortium. RESULTS: Observationally, high coffee intake was associated with low risk of obesity, metabolic syndrome and type 2 diabetes. Further, high coffee intake was associated with high body mass index, waist circumference, weight, height, systolic/diastolic blood pressure, triglycerides and total cholesterol and with low high-density lipoprotein cholesterol, but not with glucose levels. In genetic analyses, 9-10 vs 0-3 coffee-intake alleles were associated with 29% higher coffee intake. However, genetically derived high coffee intake was not associated convincingly with obesity, metabolic syndrome, type 2 diabetes, body mass index, waist circumference, weight, height, systolic/diastolic blood pressure, triglycerides, total cholesterol, high-density lipoprotein cholesterol or glucose levels. Per-allele meta-analysed odds ratios for type 2 diabetes were 1.01 (0.98-1.04) for AHR rs4410790, 0.98 (0.95-1.01) for AHR rs6968865, 1.01 (0.99-1.03) for CYP1A1/2 rs2470893, 1.01 (0.98-1.03) for CYP1A1/2 rs2472297 and 0.98 (0.95-1.01) for CYP1A1 rs2472299. CONCLUSIONS: High coffee intake was associated observationally with low risk of obesity, metabolic syndrome and type 2 diabetes, and was associated observationally with related components thereof, but with no genetic evidence to support corresponding causal relationships.
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- Authors
- Nordestgaard, A. T., Thomsen, M., & Nordestgaard, B. G.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Nordestgaard, B. G.
- Venue
- International Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-04-01
- Volume
- 44
- Issue
- 2
- Pages
- 551-565
- ISSN
- 0300-5771 (ISSN-L)
- 1464-3685
- OpenAlex
- W2159188318
- Cited by
- 189
- References
- 36
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 18 · 2023: 26 · 2022: 11 · 2021: 23 · 2020: 20 · 2019: 15 · 2018: 20 · 2017: 25 · 2016: 14 · 2015: 2
- FWCI
- 14.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Broad Institute
- Topics
- Health Sciences › Medicine › Pharmacology › Coffee research and impacts
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- coffee consumption, obesity, metabolic syndrome, type 2 diabetes, CYP1A1, CYP1A2, AHR, genetic variants, body mass index, waist circumference, serum lipids, blood pressure, triglycerides, HDL cholesterol, Mendelian randomization
- MeSH terms
- Adult, Aged, Blood Glucose, Blood Pressure, Coffee, Denmark, Diabetes Mellitus, Type 2, Female, Humans, Male, Middle Aged, Obesity, Polymorphism, Genetic, Risk Factors, Body Mass Index, Receptors, Aryl Hydrocarbon, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A2, Metabolic Syndrome, Lipid Metabolism, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Mendelian Randomization Analysis
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