Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior

Cornelis, Marilyn C.; Kacprowski, Tim; Menni, Cristina; Gustafsson, Stefan; Pivin, Edward; Adamski, Jerzy; Artati, Anna; Eap, Chin B.; Ehret, Georg; Friedrich, Nele; Ganna, Andrea; Guessous, Idris; Homuth, Georg; Lind, Lars; Magnusson, Patrik K. E.; Mangino, Massimo; Pedersen, Nancy L.; Pietzner, Maik; Suhre, Karsten; Völzke, Henry; Bochud, Murielle; Spector, Tim D.; Grabe, Hans J.; Ingelsson, Erik

doi:10.1093/hmg/ddw334

Cited by 123 publications

(160 citation statements)

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“…We conducted the analysis in 114 316 individuals from the UK Biobank study, including a subset of 48 692 individuals with 2‐hour dietary recall data, with the aims of determining the associations of coffee‐related genetic risk scores with: (1) non‐alcoholic beverage consumption (including subtypes of coffee and tea) and (2) socio‐demographic and life‐style factors. These analyses extend previously published work conducted in UK Biobank, which presented directions of effect and P ‐values of these SNPs with coffee and tea intake, but did not investigate associations with subtypes of coffee and tea or other beverages .…”

Section: Introductionsupporting

confidence: 78%

“…CYP1A2 is the enzyme responsible primarily for metabolizing caffeine and AHR affects CYP1A2 activity . It is likely that these variants affect coffee consumption through altering rate of caffeine metabolism; there is evidence that the coffee consumption‐increasing alleles of these single nucleotide polymorphisms (SNPs) decrease blood caffeine levels . Of note, five of the six additional loci (or close proxies, in or near the following genes: GCKR , ABCG2 , MLXIPL , BDNF , EFCAB5 ) have also been identified in GWAS of other phenotypes, such as body mass index and smoking initiation .…”

Section: Introductionmentioning

confidence: 99%

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Associations of coffee genetic risk scores with consumption of coffee, tea and other beverages in the UK Biobank

2017

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AimsTo evaluate the utility of coffee‐related genetic variants as proxies for coffee consumption in Mendelian randomization studies, by examining their association with non‐alcoholic beverage consumption (including subtypes of coffee and tea) and a range of socio‐demographic and life‐style factors.DesignObservational study of the association of genetic risk scores for coffee consumption with different types of non‐alcoholic beverage consumption.SettingUK general population.ParticipantsIndividuals of European ancestry aged 40–73 years from the UK Biobank between 2006 and 2010 (n = 114 316).MeasurementsGenetic risk scores were constructed using two, four and eight independent single nucleotide polymorphisms (SNPs) identified in genome‐wide association studies (GWAS) of coffee consumption. Drinks were self‐reported in a baseline questionnaire (all participants) and in detailed 24 dietary recall questionnaires in a subset (n = 48 692).FindingsGenetic risk scores explained up to 0.38, 0.19 and 0.76% of the variance in coffee, tea and combined coffee and tea consumption, respectively. Genetic risk scores demonstrated positive associations with both caffeinated and decaffeinated coffee and tea consumption, and with most subtypes of coffee consumption, but only with standard tea consumption. There was no clear evidence for positive associations with most other non‐alcoholic beverages, but higher genetic risk for coffee consumption was associated with lower daily water consumption. The genetic risk scores were associated with increased alcohol consumption, but not consistently with other socio‐demographic and life‐style factors.ConclusionsCoffee‐related genetic risk scores could be used as instruments for combined coffee and tea consumption in Mendelian randomization studies. However, associations observed with alcohol consumption require further investigation to determine whether these are due to causal effects of coffee and tea consumption or biological pleiotropy.

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Section: Introductionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Associations of coffee genetic risk scores with consumption of coffee, tea and other beverages in the UK Biobank

2017

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“…This has been shown in a GWAS of blood metabolites and of caffeine metabolites 27, 28. Caffeine is metabolized primarily by the enzyme CYP1A2 29, but does not inhibit nicotine pharmacokinetics in‐vivo nor does it alter cigarette consumption 25, 30.…”

Section: Discussionmentioning

confidence: 92%

Does coffee consumption impact on heaviness of smoking?

et al. 2017

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Background and AimsCoffee consumption and cigarette smoking are strongly associated, but whether this association is causal remains unclear. We sought to: (1) determine whether coffee consumption influences cigarette smoking causally, (2) estimate the magnitude of any association and (3) explore potential mechanisms.DesignWe used Mendelian randomization (MR) analyses of observational data, using publicly available summarized data from the Tobacco and Genetics (TAG) consortium, individual‐level data from the UK Biobank and in‐vitro experiments of candidate compounds.SettingThe TAG consortium includes data from studies in several countries. The UK Biobank includes data from men and women recruited across England, Wales and Scotland.ParticipantsThe TAG consortium provided data on n ≤ 38 181 participants. The UK Biobank provided data on 8072 participants.MeasurementsIn MR analyses, the exposure was coffee consumption (cups/day) and the outcome was heaviness of smoking (cigarettes/day). In our in‐vitro experiments we assessed the effect of caffeic acid, quercetin and p‐coumaric acid on the rate of nicotine metabolism in human liver microsomes and cDNA‐expressed human CYP2A6.FindingsTwo‐sample MR analyses of TAG consortium data indicated that heavier coffee consumption might lead to reduced heaviness of smoking [beta = −1.49, 95% confidence interval (CI) = −2.88 to −0.09]. However, in‐vitro experiments found that the compounds investigated are unlikely to inhibit significantly the rate of nicotine metabolism following coffee consumption. Further MR analyses in UK Biobank found no evidence of a causal relationship between coffee consumption and heaviness of smoking (beta = 0.20, 95% CI = –1.72 to 2.12).ConclusionsAmount of coffee consumption is unlikely to have a major causal impact upon amount of cigarette smoking. If it does influence smoking, this is not likely to operate via effects of caffeic acid, quercetin or p‐coumaric acid on nicotine metabolism. The observational association between coffee consumption and cigarette smoking may be due to smoking impacting on coffee consumption or confounding.

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“…In other words, frequent consumption of caffeine does in itself not disrupt sleep, while caffeine withdrawal actually increases sleepiness -this is what has been observed for daytime sleepiness (5). While the genetic instrument that we used for caffeine has been robustly associated with higher caffeine consumption (13), these same genetic variants are also associated with lower circulating caffeine levels (32). The most likely explanation for this is that even though these individuals consume more caffeine, they metabolise caffeine more rapidly and therefore show lower blood concentrations of caffeine and its metabolites.…”

Section: Discussionmentioning

confidence: 67%

Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours

Treur

Gibson

Taylor

et al. 2017

Preprint

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Study Objectives:Higher caffeine consumption has been linked to poorer sleep and insomnia complaints. We investigated whether these observational associations are the result of genetic risk factors influencing both caffeine consumption and poorer sleep, and/or whether they reflect (possibly bidirectional) causal effects. Methods: Summary-level data were available from genome-wide association studies (GWAS) on caffeine consumption (n=91,462), sleep duration, and chronotype (i.e., being a 'morning' versus an 'evening' person) (both n=128,266), and insomnia complaints (n=113,006). Linkage disequilibrium (LD) score regression was used to calculate genetic correlations, reflecting the extent to which genetic variants influencing caffeine consumption and sleep behaviours overlap. Causal effects were tested with bidirectional, two-sample Mendelian randomization (MR), an instrumental variable approach that utilizes genetic variants robustly associated with an exposure variable as an instrument to test causal effects. Estimates from individual genetic variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR Egger regression methods. Results: There was no clear evidence for genetic correlation between caffeine consumption and sleep duration (rg=0.000, p=0.998), chronotype (rg=0. 086, p=0.192) or insomnia (rg=-0.034, p=0.700). Two-sample Mendelian randomization analyses did not support causal effects from caffeine consumption to sleep behaviours, or the other way around. Conclusions: We found no evidence in support of genetic correlation or causal effects between caffeine consumption and sleep.While caffeine may have acute effects on sleep when taken shortly before habitual bedtime, our findings suggest that a more sustained pattern of high caffeine consumption is likely associated with poorer sleep through shared environmental factors.

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Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior

Cited by 123 publications

References 50 publications

Associations of coffee genetic risk scores with consumption of coffee, tea and other beverages in the UK Biobank

Associations of coffee genetic risk scores with consumption of coffee, tea and other beverages in the UK Biobank

Does coffee consumption impact on heaviness of smoking?

Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours

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