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Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

About this Publication
Title
Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.
Pubmed ID
25288136 (View this publication on the PubMed website)
Publication
Mol. Psychiatry. 2015 May; Volume 20 (Issue 5): Pages 647-656
Authors
Coffee and Caffeine Genetics Consortium, Cornelis MC, Byrne EM, Esko T, Nalls MA, Ganna A, Paynter N, Monda KL, Amin N, Fischer K, Renstrom F, Ngwa JS, Huikari V, Cavadino A, Nolte IM, Teumer A, Yu K, Marques-Vidal P, Rawal R, Manichaikul A, ...show more Wojczynski MK, Vink JM, Zhao JH, Burlutsky G, Lahti J, Mikkilä V, Lemaitre RN, Eriksson J, Musani SK, Tanaka T, Geller F, Luan J, Hui J, Mägi R, Dimitriou M, Garcia ME, Ho WK, Wright MJ, Rose LM, Magnusson PK, Pedersen NL, Couper D, Oostra BA, Hofman A, Ikram MA, Tiemeier HW, Uitterlinden AG, van Rooij FJ, Barroso I, Johansson I, Xue L, Kaakinen M, Milani L, Power C, Snieder H, Stolk RP, Baumeister SE, Biffar R, Gu F, Bastardot F, Kutalik Z, Jacobs DR, Forouhi NG, Mihailov E, Lind L, Lindgren C, Michaëlsson K, Morris A, Jensen M, Khaw KT, Luben RN, Wang JJ, Männistö S, Perälä MM, Kähönen M, Lehtimäki T, Viikari J, Mozaffarian D, Mukamal K, Psaty BM, Döring A, Heath AC, Montgomery GW, Dahmen N, Carithers T, Tucker KL, Ferrucci L, Boyd HA, Melbye M, Treur JL, Mellström D, Hottenga JJ, Prokopenko I, Tönjes A, Deloukas P, Kanoni S, Lorentzon M, Houston DK, Liu Y, Danesh J, Rasheed A, Mason MA, Zonderman AB, Franke L, Kristal BS, International Parkinson’s Disease Genomics Consortium (IPDGC), North American Brain Expression Consortium (NABEC), UK Brain Expression Consortium (UKBEC), Karjalainen J, Reed DR, Westra HJ, Evans MK, Saleheen D, Harris TB, Dedoussis G, Curhan G, Stumvoll M, Beilby J, Pasquale LR, Feenstra B, Bandinelli S, Ordovas JM, Chan AT, Peters U, Ohlsson C, Gieger C, Martin NG, Waldenberger M, Siscovick DS, Raitakari O, Eriksson JG, Mitchell P, Hunter DJ, Kraft P, Rimm EB, Boomsma DI, Borecki IB, Loos RJ, Wareham NJ, Vollenweider P, Caporaso N, Grabe HJ, Neuhouser ML, Wolffenbuttel BH, Hu FB, Hyppönen E, Järvelin MR, Cupples LA, Franks PW, Ridker PM, van Duijn CM, Heiss G, Metspalu A, North KE, Ingelsson E, Nettleton JA, van Dam RM, Chasman DI
Affiliations
  • Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • The University of Queensland, Queensland Brain Institute, Queensland, Australia.
  • Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Karolinska, Sweden.
  • Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
...show more
  • Institute of Health Sciences, University of Oulu, Oulu, Finland.
  • Centre for Paediatric Epidemiology and Biostatistics, Medical Research Council (MRC) Centre of Epidemiology for Child Health, University College London Institute of Child Health, London, UK.
  • Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands.
  • Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
  • Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • Institute of Genetic Epidemiology, Helmholtz Zentrum-München, Munich-Neuherberg, Germany.
  • Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
  • Washington University School of Medicine, Department of Genetics, Division of Statistical Genomics, St Louis, Missouri, USA.
  • Department of Biological Psychology / Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
  • Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, Cambridge, UK.
  • Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, New South Wales, Australia.
  • Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
  • Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.
  • Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
  • University of Mississippi Medical Center, Jackson, Mississippi, USA.
  • Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA.
  • Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark.
  • Busselton Population Medical Research Foundation Inc., Busselton, Australia.
  • Harokopio University, Athens, Greece.
  • Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, MD, USA.
  • Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK.
  • QIMR Berghofer Medical Research Institute, Queensland, Australia.
  • Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
  • Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
  • Department of Odontology, Umeå University, Umeå, Sweden.
  • Institute for Community Medicine, University Medicine Greifswald, Germany.
  • Department of Prosthodontics, Gerodontology and Biomaterials, Center of Oral Health, University Medicine Greifswald, Germany.
  • Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
  • Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
  • Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
  • Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
  • Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
  • Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
  • Department of Clinical Physiology, Tampere University Hospital and School of Medicine University of Tampere, Tampere, Finland.
  • Department of Clinical Chemistry, Fimlab Laboratories, and School of Medicine, University of Tampere, Tampere, Finland.
  • Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland.
  • Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
  • Institute of Epidemiology, Helmholtz Zentrum-München, Munich-Neuherberg, Germany.
  • Department of Psychiatry, Washington University, St.Louis, Missouri, USA.
  • Department for Psychiatry, Johannes-Gutenberg-University, Mainz, Germany.
  • School of Applied Sciences, University of Mississippi, Oxford, Mississippi, USA.
  • Clinical Laboratory & Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, USA.
  • Medical Department, University of Leipzig, Germany.
  • William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
  • Center for Non-Communicable Diseases, Pakistan.
  • Health Disparities Research Section, Clinical Research Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA.
  • Laboratory of Personality and Cognition, National Institute on Aging, NIH, Baltimore, Maryland, USA.
  • Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
  • Geriatric Unit, Azienda Sanitaria Firenze, Florence, Italy.
  • Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA.
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Research Unit of Molecular Epidemiology, Helmholtz Zentrum-München, Munich-Neuherberg, Germany.
  • Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Turku University Hospital, Turku, Finland.
  • Folkhälsan Research Centre, Helsinki, Finland.
  • Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, USA.
  • Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS Hospital Stralsund, Germany.
  • Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
Abstract

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

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