{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:12:36Z","timestamp":1791821556730,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T00:00:00Z","timestamp":1567555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and objectives<\/jats:title><jats:p>Coffee intake is associated with low risk of symptomatic gallstone disease (<jats:styled-content style=\"fixed-case\">GSD<\/jats:styled-content>). We tested the hypothesis that high coffee intake causally protects against symptomatic <jats:styled-content style=\"fixed-case\">GSD<\/jats:styled-content> using a Mendelian randomization design.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First, we tested whether high coffee intake was associated with low risk of <jats:styled-content style=\"fixed-case\">GSD<\/jats:styled-content> in 104\u00a0493 individuals from the general population. Mean follow\u2010up was 8\u00a0years (range:\u00a0&lt;1\u201313\u00a0years). Secondly, we tested whether two genetic variants near <jats:italic><jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A1\/A2<\/jats:italic> (rs2472297) and <jats:italic><jats:styled-content style=\"fixed-case\">AHR<\/jats:styled-content><\/jats:italic> (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 <jats:styled-content style=\"fixed-case\">GSD<\/jats:styled-content> in 114\u00a0220 individuals including 7294 gallstone events. Mean follow\u2010up was 38\u00a0years (range: &lt;1\u201340\u00a0years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In observational analysis, those with coffee intake of &gt;6 cups daily had 23% lower risk of <jats:styled-content style=\"fixed-case\">GSD<\/jats:styled-content> compared to individuals without coffee intake [hazard ratio (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>)\u00a0=\u00a00.77 (95% confidence interval: 0.61\u20130.94)]. 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 (<jats:italic>P<\/jats:italic> for trend\u00a0=\u00a03\u00a0x\u00a010<jats:sup>\u2212178<\/jats:sup>) and a corresponding stepwise lower risk of <jats:styled-content style=\"fixed-case\">GSD<\/jats:styled-content> up to 19%[<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\u00a0=\u00a00.81 (0.69\u20130.96)]. The estimated observational odds ratio for <jats:styled-content style=\"fixed-case\">GSD<\/jats:styled-content> for a one cup per day higher coffee intake was 0.97 (0.96\u20130.98), equal to 3% lower risk. The corresponding genetic odds ratio was 0.89 (0.83\u20130.95), equal to 11% lower risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>High coffee intake is associated observationally with low risk of GSD, and with genetic evidence to support a causal relationship.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12970","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T04:02:03Z","timestamp":1567656123000},"page":"42-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Coffee intake protects against symptomatic gallstone disease in the general population: a Mendelian randomization study"],"prefix":"10.1111","volume":"287","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5500-686X","authenticated-orcid":false,"given":"A. 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