Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior
Cornelis MC, Kacprowski T, Menni C, Gustafsson S, Pivin E, Adamski J, Artati A, Eap CB, Ehret G, Friedrich N, Ganna A, Guessous I, Homuth G, Lind L, Magnusson PK, Mangino M, Pedersen NL, Pietzner M, Suhre K, Völzke H, Swiss Kidney Project on Genes in Hypertension (SKIPOGH) team, Bochud M, Spector TD, Grabe HJ, Ingelsson E
Human molecular genetics · 158 citations
How it was studied
- Design
- Meta-analysis (classified by our AI screen)
- Studied in
- People
- Main outcome
- No health outcome
Who paid for it
- Funding
- Possibly industry funded
- Government
- National Science Foundation
- Nonprofit
- American Diabetes Association
- University or hospital
- Northwestern University
- Nonprofit
- Qatar Foundation
- Government
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Government
- Bundesministerium für Bildung und Forschung
- University or hospital
- Universität Greifswald
- University or hospital
- Weill Cornell Medical College
- Company
- Quest High Performance Computing
- University or hospital
- Weill Cornell Medicine - Qatar
- Government
- Medical Research Council
- Grants
- Bundesministerium für Bildung und Forschung (01 ZZ0103); American Diabetes Association (7–13‐JF‐15); Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (124087); Bundesministerium für Bildung und Forschung (01 ZZ 0403); Bundesministerium für Bildung und Forschung (03ZIK012); Bundesministerium für Bildung und Forschung (01ZZ9603)
Based on 11 listed funder(s).
Publication
- Published
- 2016-09-29 · Hum Mol Genet · vol. 25 · issue 24 · p. ddw334
- Publisher
- Oxford University Press
- Cited
- 189 citations · more than 99% of similar papers · 12.2× the field average
- Impact
- Top 10% most cited in its field
- References
- 54 works
- Access
- Free to read
- Research areas
- Coffee research and impacts · Folate and B Vitamins Research · Nutritional Studies and Diet
- Keywords
- Paraxanthine, Caffeine, Theobromine, Genome-wide association study, Theophylline, Single-nucleotide polymorphism, Biology, Metabolome, Genetics, Pharmacology, Metabolomics, Metabolism, CYP1A2, Endocrinology, Bioinformatics, Gene, Genotype, Cytochrome P450
- MeSH
- humans, caffeine, theobromine, theophylline, cytochrome p-450 cyp1a2, immunoglobulins, membrane glycoproteins, receptors, aryl hydrocarbon, antigens, cd, polymorphism, single nucleotide, coffee, female, male, genome-wide association study, cytochrome p-450 cyp2a6, white people, cd83 antigen, basic helix-loop-helix proteins
25 authors
From US, DE, GB, SE, CH, QA
- Marilyn C. Cornelis · correspondingNorthwestern University
- Tim KacprowskiUniversität Greifswald; German Centre for Cardiovascular Research
- Cristina MenniSt Thomas' Hospital; King's College London
- Stefan GustafssonUppsala University; Science for Life Laboratory
- Edward PivinCentre Hospitalier Universitaire Vaudois; Institute of Social and Preventive Medicine
- Jerzy AdamskiHelmholtz Munich; Deutsches Diabetes-Zentrum e.V.; German Center for Diabetes Research; Heinrich Heine University Düsseldorf; Technical University of Munich
Abstract
Caffeine is the most widely consumed psychoactive substance in the world and presents with wide interindividual variation in metabolism. This variation may modify potential adverse or beneficial effects of caffeine on health. We conducted a genome-wide association study (GWAS) of plasma caffeine, paraxanthine, theophylline, theobromine and paraxanthine/caffeine ratio among up to 9,876 individuals of European ancestry from six population-based studies. A single SNP at 6p23 (near CD83) and several SNPs at 7p21 (near AHR), 15q24 (near CYP1A2) and 19q13.2 (near CYP2A6) met GW-significance (P < 5 × 10-8) and were associated with one or more metabolites. Variants at 7p21 and 15q24 associated with higher plasma caffeine and lower plasma paraxanthine/caffeine (slow caffeine metabolism) were previously associated with lower coffee and caffeine consumption behavior in GWAS. Variants at 19q13.2 associated with higher plasma paraxanthine/caffeine (slow paraxanthine metabolism) were also associated with lower coffee consumption in the UK Biobank (n = 94 343, P < 1.0 × 10-6). Variants at 2p24 (in GCKR), 4q22 (in ABCG2) and 7q11.23 (near POR) that were previously associated with coffee consumption in GWAS were nominally associated with plasma caffeine or its metabolites. Taken together, we have identified genetic factors contributing to variation in caffeine metabolism and confirm an important modulating role of systemic caffeine levels in dietary caffeine consumption behavior. Moreover, candidate genes identified encode proteins with important clinical functions that extend beyond caffeine metabolism.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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