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Coffee intake protects against symptomatic gallstone disease in the general population: a Mendelian randomization study

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@article{fe5c3894062c47c6b63ede3313bf5ad5,
title = "Coffee intake protects against symptomatic gallstone disease in the general population: a Mendelian randomization study",
abstract = "BACKGROUND AND OBJECTIVES: Coffee intake is associated with low risk of symptomatic gallstone disease (GSD). We tested the hypothesis that high coffee intake causally protects against symptomatic GSD using a Mendelian randomization design.METHODS: First, we tested whether high coffee intake was associated with low risk of GSD in 104 493 individuals from the general population. Mean follow-up was 8 years (range: <1-13 years). Secondly, we tested whether two genetic variants near CYP1A1/A2 (rs2472297) and AHR (rs4410790), combined as an allele score, were associated with higher coffee intake measured as a continuous variable. Thirdly, we tested whether the allele score was associated with lower risk of GSD in 114 220 individuals including 7294 gallstone events. Mean follow-up was 38 years (range: <1-40 years).RESULTS: In observational analysis, those with coffee intake of >6 cups daily had 23{\%} lower risk of GSD compared to individuals without coffee intake [hazard ratio (HR) = 0.77 (95{\%} confidence interval: 0.61-0.94)]. In genetic analysis, there was a stepwise higher coffee intake of up to 41{\%} (caffeine per day) in individuals with 4 (highest) versus 0 (lowest) coffee intake alleles (P for trend = 3 x 10-178 ) and a corresponding stepwise lower risk of GSD up to 19{\%}[HR = 0.81 (0.69-0.96)]. The estimated observational odds ratio for GSD for a one cup per day higher coffee intake was 0.97 (0.96-0.98), equal to 3{\%} lower risk. The corresponding genetic odds ratio was 0.89 (0.83-0.95), equal to 11{\%} lower risk.CONCLUSION: High coffee intake is associated observationally with low risk of GSD, and with genetic evidence to support a causal relationship.",
author = "Nordestgaard, {A T} and S Stender and Nordestgaard, {B G} and A Tybjaerg-Hansen",
note = "{\circledC} 2019 The Association for the Publication of the Journal of Internal Medicine.",
year = "2020",
month = "1",
doi = "10.1111/joim.12970",
language = "English",
volume = "287",
pages = "42--53",
journal = "Journal of Internal Medicine",
issn = "0954-6820",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Coffee intake protects against symptomatic gallstone disease in the general population

T2 - a Mendelian randomization study

AU - Nordestgaard, A T

AU - Stender, S

AU - Nordestgaard, B G

AU - Tybjaerg-Hansen, A

N1 - © 2019 The Association for the Publication of the Journal of Internal Medicine.

PY - 2020/1

Y1 - 2020/1

N2 - BACKGROUND AND OBJECTIVES: Coffee intake is associated with low risk of symptomatic gallstone disease (GSD). We tested the hypothesis that high coffee intake causally protects against symptomatic GSD using a Mendelian randomization design.METHODS: First, we tested whether high coffee intake was associated with low risk of GSD in 104 493 individuals from the general population. Mean follow-up was 8 years (range: <1-13 years). Secondly, we tested whether two genetic variants near CYP1A1/A2 (rs2472297) and AHR (rs4410790), combined as an allele score, were associated with higher coffee intake measured as a continuous variable. Thirdly, we tested whether the allele score was associated with lower risk of GSD in 114 220 individuals including 7294 gallstone events. Mean follow-up was 38 years (range: <1-40 years).RESULTS: In observational analysis, those with coffee intake of >6 cups daily had 23% lower risk of GSD compared to individuals without coffee intake [hazard ratio (HR) = 0.77 (95% confidence interval: 0.61-0.94)]. In genetic analysis, there was a stepwise higher coffee intake of up to 41% (caffeine per day) in individuals with 4 (highest) versus 0 (lowest) coffee intake alleles (P for trend = 3 x 10-178 ) and a corresponding stepwise lower risk of GSD up to 19%[HR = 0.81 (0.69-0.96)]. The estimated observational odds ratio for GSD for a one cup per day higher coffee intake was 0.97 (0.96-0.98), equal to 3% lower risk. The corresponding genetic odds ratio was 0.89 (0.83-0.95), equal to 11% lower risk.CONCLUSION: High coffee intake is associated observationally with low risk of GSD, and with genetic evidence to support a causal relationship.

AB - BACKGROUND AND OBJECTIVES: Coffee intake is associated with low risk of symptomatic gallstone disease (GSD). We tested the hypothesis that high coffee intake causally protects against symptomatic GSD using a Mendelian randomization design.METHODS: First, we tested whether high coffee intake was associated with low risk of GSD in 104 493 individuals from the general population. Mean follow-up was 8 years (range: <1-13 years). Secondly, we tested whether two genetic variants near CYP1A1/A2 (rs2472297) and AHR (rs4410790), combined as an allele score, were associated with higher coffee intake measured as a continuous variable. Thirdly, we tested whether the allele score was associated with lower risk of GSD in 114 220 individuals including 7294 gallstone events. Mean follow-up was 38 years (range: <1-40 years).RESULTS: In observational analysis, those with coffee intake of >6 cups daily had 23% lower risk of GSD compared to individuals without coffee intake [hazard ratio (HR) = 0.77 (95% confidence interval: 0.61-0.94)]. In genetic analysis, there was a stepwise higher coffee intake of up to 41% (caffeine per day) in individuals with 4 (highest) versus 0 (lowest) coffee intake alleles (P for trend = 3 x 10-178 ) and a corresponding stepwise lower risk of GSD up to 19%[HR = 0.81 (0.69-0.96)]. The estimated observational odds ratio for GSD for a one cup per day higher coffee intake was 0.97 (0.96-0.98), equal to 3% lower risk. The corresponding genetic odds ratio was 0.89 (0.83-0.95), equal to 11% lower risk.CONCLUSION: High coffee intake is associated observationally with low risk of GSD, and with genetic evidence to support a causal relationship.

U2 - 10.1111/joim.12970

DO - 10.1111/joim.12970

M3 - Journal article

VL - 287

SP - 42

EP - 53

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 0954-6820

IS - 1

ER -

ID: 59307516