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 citas
Cómo se estudió
- Diseño
- Metaanálisis (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas
- Resultado principal
- Sin resultado de salud
Quién lo pagó
- Financiación
- Posiblemente financiado por la industria
- Gobierno
- National Science Foundation
- Organización sin fines de lucro
- American Diabetes Association
- Universidad u hospital
- Northwestern University
- Organización sin fines de lucro
- Qatar Foundation
- Gobierno
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Gobierno
- Bundesministerium für Bildung und Forschung
- Universidad u hospital
- Universität Greifswald
- Universidad u hospital
- Weill Cornell Medical College
- Empresa
- Quest High Performance Computing
- Universidad u hospital
- Weill Cornell Medicine - Qatar
- Gobierno
- Medical Research Council
- Subvenciones
- 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)
Según 11 financiadores declarados.
Publicación
- Publicado
- 2016-09-29 · Hum Mol Genet · vol. 25 · número 24 · pág. ddw334
- Editorial
- Oxford University Press
- Citado
- 189 citas · más que el 99% de estudios similares · 12.2× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 54 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Coffee research and impacts · Folate and B Vitamins Research · Nutritional Studies and Diet
- Palabras clave
- 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 autores
- Marilyn C. Cornelis🇺🇸 · autor de correspondenciaNorthwestern University
- Tim Kacprowski🇩🇪Universität Greifswald; German Centre for Cardiovascular Research
- Cristina Menni🇬🇧St Thomas' Hospital; King's College London
- Stefan Gustafsson🇸🇪Uppsala University; Science for Life Laboratory
- Edward Pivin🇨🇭Centre Hospitalier Universitaire Vaudois; Institute of Social and Preventive Medicine
- Jerzy Adamski🇩🇪Helmholtz Munich; Deutsches Diabetes-Zentrum e.V.; German Center for Diabetes Research; Heinrich Heine University Düsseldorf; Technical University of Munich
- Anna Artati🇩🇪Helmholtz Munich
- Chin B. Eap🇨🇭University of Geneva; University of Lausanne
- Georg Ehret🇺🇸🇨🇭Johns Hopkins University; University Hospital of Geneva
- Nele Friedrich🇩🇪Universitätsmedizin Greifswald; German Centre for Cardiovascular Research
- Andrea Ganna🇺🇸Broad Institute; Harvard University; Massachusetts General Hospital
- Idris Guessous🇺🇸🇨🇭Emory University; Centre Hospitalier Universitaire Vaudois; University Hospital of Geneva; Institute of Social and Preventive Medicine
- Georg Homuth🇩🇪Universität Greifswald
- Lars Lind🇸🇪Uppsala University
- Patrik K. E. Magnusson🇸🇪Karolinska Institutet
- Massimo Mangino🇬🇧St Thomas' Hospital; King's College London
- Nancy L. Pedersen🇸🇪Karolinska Institutet
- Maik Pietzner🇩🇪Universitätsmedizin Greifswald; German Centre for Cardiovascular Research
- Karsten Suhre🇩🇪🇶🇦Helmholtz Munich; Institute of Bioinformatics and Systems Biology; Weill Cornell Medical College in Qatar
- Henry Völzke🇩🇪Universitätsmedizin Greifswald
- Swiss Kidney Project on Genes in Hypertension (SKIPOGH) team🇨🇭Centre Hospitalier Universitaire Vaudois; Institute of Social and Preventive Medicine
- Murielle Bochud🇬🇧🇨🇭St Thomas' Hospital; King's College London; Centre Hospitalier Universitaire Vaudois; Institute of Social and Preventive Medicine
- Tim D. Spector🇬🇧🇩🇪St Thomas' Hospital; King's College London; Universitätsmedizin Greifswald
- Hans Jörgen Grabe🇸🇪🇩🇪🇺🇸Uppsala University; Universitätsmedizin Greifswald; Science for Life Laboratory; Stanford University
- Erik Ingelsson🇸🇪🇺🇸Uppsala University; Science for Life Laboratory; Stanford University
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
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