Review

. 2015 May;20(5):647-656.

doi: 10.1038/mp.2014.107. Epub 2014 Oct 7.

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

Coffee and Caffeine Genetics Consortium; Marilyn C Cornelis^{1

2}, Enda M Byrne^#³, Tõnu Esko^#^{4

5

6

7}, Michael A Nalls^#⁸, Andrea Ganna⁹, Nina Paynter¹⁰, Keri L Monda¹¹, Najaf Amin¹², Krista Fischer⁴, Frida Renstrom¹³, Julius S Ngwa¹⁴, Ville Huikari¹⁵, Alana Cavadino¹⁶, Ilja M Nolte¹⁷, Alexander Teumer¹⁸, Kai Yu¹⁹, Pedro Marques-Vidal²⁰, Rajesh Rawal²¹, Ani Manichaikul²², Mary K Wojczynski²³, Jacqueline M Vink²⁴, Jing Hua Zhao²⁵, George Burlutsky²⁶, Jari Lahti^{27

28}, Vera Mikkilä^{29

30}, Rozenn N Lemaitre³¹, Joel Eriksson³², Solomon K Musani³³, Toshiko Tanaka³⁴, Frank Geller³⁵, Jian'an Luan²⁵, Jennie Hui^{36

37

38

39}, Reedik Mägi⁴, Maria Dimitriou⁴⁰, Melissa E Garcia⁴¹, Weang-Kee Ho⁴², Margaret J Wright⁴³, Lynda M Rose¹⁰, Patrik Ke Magnusson⁹, Nancy L Pedersen⁹, David Couper⁴⁴, Ben A Oostra⁴⁵, Albert Hofman¹², Mohammad Arfan Ikram^{12

46

47}, Henning W Tiemeier^{12

48}, Andre G Uitterlinden^{12

49}, Frank Ja van Rooij¹², Inês Barroso^{50

51}, Ingegerd Johansson⁵², Luting Xue¹⁴, Marika Kaakinen^{15

53

54}, Lili Milani⁴, Chris Power¹⁶, Harold Snieder¹⁷, Ronald P Stolk¹⁷, Sebastian E Baumeister⁵⁵, Reiner Biffar⁵⁶, Fangyi Gu¹⁹, François Bastardot⁵⁷, Zoltán Kutalik^{58

59

60}, David R Jacobs Jr⁶¹, Nita G Forouhi²⁵, Evelin Mihailov⁴, Lars Lind⁶², Cecilia Lindgren⁶³, Karl Michaëlsson⁶⁴, Andrew Morris⁶³, Majken Jensen², Kay-Tee Khaw⁴², Robert N Luben⁴², Jie Jin Wang²⁶, Satu Männistö⁶⁵, Mia-Maria Perälä⁶⁵, Mika Kähönen⁶⁶, Terho Lehtimäki⁶⁷, Jorma Viikari⁶⁸, Dariush Mozaffarian^{1

2

69}, Kenneth Mukamal⁷⁰, Bruce M Psaty^{31

71

72

73}, Angela Döring⁷⁴, Andrew C Heath⁷⁵, Grant W Montgomery⁴³, Norbert Dahmen⁷⁶, Teresa Carithers⁷⁷, Katherine L Tucker⁷⁸, Luigi Ferrucci³⁴, Heather A Boyd³⁵, Mads Melbye³⁵, Jorien L Treur²⁴, Dan Mellström³², Jouke Jan Hottenga²⁴, Inga Prokopenko^{63

79}, Anke Tönjes^{80

81}, Panos Deloukas^{50

82

83}, Stavroula Kanoni⁸², Mattias Lorentzon³², Denise K Houston⁸⁴, Yongmei Liu⁸⁴, John Danesh⁴², Asif Rasheed⁸⁵, Marc A Mason⁸⁶, Alan B Zonderman⁸⁷, Lude Franke⁸⁸, Bruce S Kristal^{89

90}; International Parkinson’s Disease Genomics Consortium (IPDGC); North American Brain Expression Consortium (NABEC); UK Brain Expression Consortium (UKBEC); Juha Karjalainen⁸⁸, Danielle R Reed⁹¹, Harm-Jan Westra⁸⁸, Michele K Evans⁸⁶, Danish Saleheen^{42

85}, Tamara B Harris⁴¹, George Dedoussis⁴⁰, Gary Curhan¹, Michael Stumvoll^{80

81}, John Beilby^{36

37

38}, Louis R Pasquale^{1

92}, Bjarke Feenstra³⁵, Stefania Bandinelli⁹³, Jose M Ordovas⁹⁴, Andrew T Chan^{1

95}, Ulrike Peters⁹⁶, Claes Ohlsson³², Christian Gieger²¹, Nicholas G Martin⁴³, Melanie Waldenberger⁹⁷, David S Siscovick^{31

71}, Olli Raitakari^{30

98}, Johan G Eriksson^{28

99

100}, Paul Mitchell²⁶, David J Hunter^{1

101}, Peter Kraft¹⁰¹, Eric B Rimm^{1

2

69}, Dorret I Boomsma²⁴, Ingrid B Borecki²³, Ruth Jf Loos^{25

102

103}, Nicholas J Wareham²⁵, Peter Vollenweider⁵⁷, Neil Caporaso¹⁹, Hans Jörgen Grabe¹⁰⁴, Marian L Neuhouser¹⁰⁵, Bruce Hr Wolffenbuttel¹⁰⁶, Frank B Hu^{1

2

69}, Elina Hyppönen^{16

107

108}, Marjo-Riitta Järvelin^{15

53

54

109

110}, L Adrienne Cupples^{14

111}, Paul W Franks^{2

13

112}, Paul M Ridker¹⁰, Cornelia M van Duijn^{12

113}, Gerardo Heiss¹¹, Andres Metspalu⁴, Kari E North¹¹, Erik Ingelsson^{62

63}, Jennifer A Nettleton¹¹⁴, Rob M van Dam¹¹⁵, Daniel I Chasman¹⁰

Collaborators, Affiliations

Collaborators

Michael A Nalls, Vincent Plagnol, Dena G Hernandez, Manu Sharma, Una-Marie Sheerin, Mohamad Saad, Javier Simón-Sánchez, Claudia Schulte, Suzanne Lesage, Sigurlaug Sveinbjörnsdóttir, Sampath Arepalli, Roger Barker, Yoav Ben-Shlomo, Henk W Berendse, Daniela Berg, Kailash Bhatia, Rob M A de Bie, Alessandro Biffi, Bas Bloem, Zoltan Bochdanovits, Michael Bonin, M Bras, Kathrin Brockmann, Janet Brooks, David J Burn, Gavin Charlesworth, Honglei Chen, Patrick F Chinnery, Sean Chong, Carl E Clarke, Mark R Cookson, J Mark Cooper, Jean Christophe Corvol, Carl Counsell, Philippe Damier, Jean-François Dartigues, Panos Deloukas, Günther Deuschl, David T Dexter, Karin D van Dijk, Allissa Dillman, Frank Durif, Alexandra Dürr, Sarah Edkins, Jonathan R Evans, Thomas Foltynie, Jing Dong, Michelle Gardner, J Raphael Gibbs, Alison Goate, Emma Gray, Rita Guerreiro, Clare Harris, Jacobus J van Hilten, Albert Hofman, Albert Hollenbeck, Janice Holton, Michele Hu, Xuemei Huang, Milton S Hershey, Isabel Wurster, Walter Mätzler, Gavin Hudson, Sarah E Hunt, Johanna Huttenlocher, Thomas Illig, Helmholtz Zentrum München, Pálmi V Jónsson, Jean-Charles Lambert, Cordelia Langford, Andrew Lees, Peter Lichtner, Helmholtz Zentrum München, Patricia Limousin, Grisel Lopez, Delia Lorenz, Alisdair McNeill, Catriona Moorby, Matthew Moore, Huw R Morris, Karen E Morrison, Sean S O' Sullivan, Justin Pearson, Joel S Perlmutter, Hjörvar Pétursson, Pierre Pollak, Simon Potter, Bernard Ravina, Tamas Revesz, Olaf Riess, Fernando Rivadeneira, Patrizia Rizzu, Mina Ryten, Stephen Sawcer, Anthony Schapira, Hans Scheffer, Karen Shaw, Ellen Sidransky, Colin Smith, Chris C A Spencer, Hreinn Stefánsson, Francesco Bettella, Joanna D Stockton, Amy Strange, Kevin Talbot, M Tanner, Avazeh Tashakkori-Ghanbaria, François Tison, Daniah Trabzuni, Bryan J Traynor, André G Uitterlinden, Daan Velseboer, Marie Vidailhet, Robert Walker, Bart van de Warrenburg, Mirdhu Wickremaratchi, Nigel Williams, Caroline H Williams-Gray, Sophie Winder-Rhodes, Kári Stefánsson, Maria Martinez, Paul Sabatier, Nicholas W Wood, John Hardy, Peter Heutink, Alexis Brice, Thomas Gasser, Andrew B Singleton, Andrew Singleton, Mark Cookson, J Raphael Gibbs, Dena Hernandez, Allissa Dillman, Michael Nalls, Alan Zonderman, Sampath Arepalli, Luigi Ferrucci, Robert Johnson, Dan Longo, Richard O'Brien, Bryan Traynor, Juan Troncoso, Marcel van der Brug, Ronald Zielke, John Hardy, Michael Weale, Mina Ryten, Adaikalavan Ramasamy, Daniah Trabzuni, P O Box, Colin Smith, Robert Walker

Affiliations

¹ Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
³ The University of Queensland, Queensland Brain Institute, Queensland, Australia.
⁴ Estonian Genome Center, University of Tartu, Tartu, Estonia.
⁵ Division of Endocrinology, Children's Hospital Boston, Boston, Massachusetts, USA.
⁶ Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
⁷ Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
⁸ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA.
⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Karolinska, Sweden.
¹⁰ Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
¹² Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
¹³ Department of Clinical Sciences, Lund University, Malmö, Sweden.
¹⁴ Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
¹⁵ Institute of Health Sciences, University of Oulu, Oulu, Finland.
¹⁶ 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.
¹⁷ Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands.
¹⁸ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany.
¹⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
²⁰ Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
²¹ Institute of Genetic Epidemiology, Helmholtz Zentrum-München, Munich-Neuherberg, Germany.
²² Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
²³ Washington University School of Medicine, Department of Genetics, Division of Statistical Genomics, St Louis, Missouri, USA.
²⁴ Department of Biological Psychology / Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
²⁵ Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, Cambridge, UK.
²⁶ Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, New South Wales, Australia.
²⁷ Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
²⁸ Folkhälsan Research Centre, Helsinki, Finland.
²⁹ Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.
³⁰ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Turku University Hospital, Turku, Finland.
³¹ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
³² Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
³³ University of Mississippi Medical Center, Jackson, Mississippi, USA.
³⁴ Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA.
³⁵ Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark.
³⁶ Busselton Population Medical Research Foundation Inc., Busselton, Australia.
³⁷ PathWest Laboratory Medicine WA, Nedlands, Western Australia.
³⁸ School of Pathology & Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia.
³⁹ School of Population Health, The University of Western Australia, Nedlands, Western Australia.
⁴⁰ Harokopio University, Athens, Greece.
⁴¹ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, MD, USA.
⁴² Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK.
⁴³ QIMR Berghofer Medical Research Institute, Queensland, Australia.
⁴⁴ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁴⁵ Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
⁴⁶ Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands.
⁴⁷ Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
⁴⁸ Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
⁴⁹ Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
⁵⁰ Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
⁵¹ University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
⁵² Department of Odontology, Umeå University, Umeå, Sweden.
⁵³ Biocenter Oulu, University of Oulu, Oulu, Finland.
⁵⁴ Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, UK.
⁵⁵ Institute for Community Medicine, University Medicine Greifswald, Germany.
⁵⁶ Department of Prosthodontics, Gerodontology and Biomaterials, Center of Oral Health, University Medicine Greifswald, Germany.
⁵⁷ Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
⁵⁸ Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
⁵⁹ Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
⁶⁰ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁶¹ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
⁶² Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
⁶³ Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
⁶⁴ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
⁶⁵ Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
⁶⁶ Department of Clinical Physiology, Tampere University Hospital and School of Medicine University of Tampere, Tampere, Finland.
⁶⁷ Department of Clinical Chemistry, Fimlab Laboratories, and School of Medicine, University of Tampere, Tampere, Finland.
⁶⁸ Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland.
⁶⁹ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
⁷⁰ Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
⁷¹ Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, USA.
⁷² Department of Health Services, University of Washington, Seattle, Washington, USA.
⁷³ Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.
⁷⁴ Institute of Epidemiology, Helmholtz Zentrum-München, Munich-Neuherberg, Germany.
⁷⁵ Department of Psychiatry, Washington University, St.Louis, Missouri, USA.
⁷⁶ Department for Psychiatry, Johannes-Gutenberg-University, Mainz, Germany.
⁷⁷ School of Applied Sciences, University of Mississippi, Oxford, Mississippi, USA.
⁷⁸ Clinical Laboratory & Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, USA.
⁷⁹ Department of Genomics of Common Diseases, Imperial College London, London, UK.
⁸⁰ Medical Department, University of Leipzig, Germany.
⁸¹ IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.
⁸² William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁸³ King Abdulaziz University, Jeddah, Saudi Arabia.
⁸⁴ Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁸⁵ Center for Non-Communicable Diseases, Pakistan.
⁸⁶ Health Disparities Research Section, Clinical Research Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA.
⁸⁷ Laboratory of Personality and Cognition, National Institute on Aging, NIH, Baltimore, Maryland, USA.
⁸⁸ Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁸⁹ Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁹⁰ Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
⁹¹ Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
⁹² Mass Eye and Ear Infirmary, Boston, Massachusetts, USA.
⁹³ Geriatric Unit, Azienda Sanitaria Firenze, Florence, Italy.
⁹⁴ Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA.
⁹⁵ Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁹⁶ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
⁹⁷ Research Unit of Molecular Epidemiology, Helmholtz Zentrum-München, Munich-Neuherberg, Germany.
⁹⁸ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁹⁹ Department of General Practice and Primary health Care, University of Helsinki, Helsinki, Finland.
¹⁰⁰ Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.
¹⁰¹ Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, USA.
¹⁰² The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁰³ The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁰⁴ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS Hospital Stralsund, Germany.
¹⁰⁵ Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
¹⁰⁶ Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁰⁷ School of Population Health, University of South Australia, Adelaide, Australia.
¹⁰⁸ South Australian Health and Medical Research Institute, Adelaide, Australia.
¹⁰⁹ Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland.
¹¹⁰ Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
¹¹¹ The Framingham Heart Study, Framingham, Massachusetts, USA.
¹¹² Department of Public Health & Clinical Medicine, Section for Medicine, Umeå University, Umeå, Sweden.
¹¹³ Netherlands Consortium for Healthy Ageing and National Genomics Initiative, Leiden, The Netherlands.
¹¹⁴ Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, Texas, USA.
¹¹⁵ 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.

^# Contributed equally.

PMID: 25288136
PMCID: PMC4388784
DOI: 10.1038/mp.2014.107

Review

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

Coffee and Caffeine Genetics Consortium et al. Mol Psychiatry. 2015 May.

. 2015 May;20(5):647-656.

doi: 10.1038/mp.2014.107. Epub 2014 Oct 7.

Authors

Collaborators

Michael A Nalls, Vincent Plagnol, Dena G Hernandez, Manu Sharma, Una-Marie Sheerin, Mohamad Saad, Javier Simón-Sánchez, Claudia Schulte, Suzanne Lesage, Sigurlaug Sveinbjörnsdóttir, Sampath Arepalli, Roger Barker, Yoav Ben-Shlomo, Henk W Berendse, Daniela Berg, Kailash Bhatia, Rob M A de Bie, Alessandro Biffi, Bas Bloem, Zoltan Bochdanovits, Michael Bonin, M Bras, Kathrin Brockmann, Janet Brooks, David J Burn, Gavin Charlesworth, Honglei Chen, Patrick F Chinnery, Sean Chong, Carl E Clarke, Mark R Cookson, J Mark Cooper, Jean Christophe Corvol, Carl Counsell, Philippe Damier, Jean-François Dartigues, Panos Deloukas, Günther Deuschl, David T Dexter, Karin D van Dijk, Allissa Dillman, Frank Durif, Alexandra Dürr, Sarah Edkins, Jonathan R Evans, Thomas Foltynie, Jing Dong, Michelle Gardner, J Raphael Gibbs, Alison Goate, Emma Gray, Rita Guerreiro, Clare Harris, Jacobus J van Hilten, Albert Hofman, Albert Hollenbeck, Janice Holton, Michele Hu, Xuemei Huang, Milton S Hershey, Isabel Wurster, Walter Mätzler, Gavin Hudson, Sarah E Hunt, Johanna Huttenlocher, Thomas Illig, Helmholtz Zentrum München, Pálmi V Jónsson, Jean-Charles Lambert, Cordelia Langford, Andrew Lees, Peter Lichtner, Helmholtz Zentrum München, Patricia Limousin, Grisel Lopez, Delia Lorenz, Alisdair McNeill, Catriona Moorby, Matthew Moore, Huw R Morris, Karen E Morrison, Sean S O' Sullivan, Justin Pearson, Joel S Perlmutter, Hjörvar Pétursson, Pierre Pollak, Simon Potter, Bernard Ravina, Tamas Revesz, Olaf Riess, Fernando Rivadeneira, Patrizia Rizzu, Mina Ryten, Stephen Sawcer, Anthony Schapira, Hans Scheffer, Karen Shaw, Ellen Sidransky, Colin Smith, Chris C A Spencer, Hreinn Stefánsson, Francesco Bettella, Joanna D Stockton, Amy Strange, Kevin Talbot, M Tanner, Avazeh Tashakkori-Ghanbaria, François Tison, Daniah Trabzuni, Bryan J Traynor, André G Uitterlinden, Daan Velseboer, Marie Vidailhet, Robert Walker, Bart van de Warrenburg, Mirdhu Wickremaratchi, Nigel Williams, Caroline H Williams-Gray, Sophie Winder-Rhodes, Kári Stefánsson, Maria Martinez, Paul Sabatier, Nicholas W Wood, John Hardy, Peter Heutink, Alexis Brice, Thomas Gasser, Andrew B Singleton, Andrew Singleton, Mark Cookson, J Raphael Gibbs, Dena Hernandez, Allissa Dillman, Michael Nalls, Alan Zonderman, Sampath Arepalli, Luigi Ferrucci, Robert Johnson, Dan Longo, Richard O'Brien, Bryan Traynor, Juan Troncoso, Marcel van der Brug, Ronald Zielke, John Hardy, Michael Weale, Mina Ryten, Adaikalavan Ramasamy, Daniah Trabzuni, P O Box, Colin Smith, Robert Walker

Affiliations

¹ Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
³ The University of Queensland, Queensland Brain Institute, Queensland, Australia.
⁴ Estonian Genome Center, University of Tartu, Tartu, Estonia.
⁵ Division of Endocrinology, Children's Hospital Boston, Boston, Massachusetts, USA.
⁶ Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
⁷ Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
⁸ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA.
⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Karolinska, Sweden.
¹⁰ Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
¹² Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
¹³ Department of Clinical Sciences, Lund University, Malmö, Sweden.
¹⁴ Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
¹⁵ Institute of Health Sciences, University of Oulu, Oulu, Finland.
¹⁶ 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.
¹⁷ Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands.
¹⁸ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany.
¹⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
²⁰ Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
²¹ Institute of Genetic Epidemiology, Helmholtz Zentrum-München, Munich-Neuherberg, Germany.
²² Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
²³ Washington University School of Medicine, Department of Genetics, Division of Statistical Genomics, St Louis, Missouri, USA.
²⁴ Department of Biological Psychology / Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
²⁵ Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, Cambridge, UK.
²⁶ Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, New South Wales, Australia.
²⁷ Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
²⁸ Folkhälsan Research Centre, Helsinki, Finland.
²⁹ Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.
³⁰ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Turku University Hospital, Turku, Finland.
³¹ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
³² Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
³³ University of Mississippi Medical Center, Jackson, Mississippi, USA.
³⁴ Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA.
³⁵ Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark.
³⁶ Busselton Population Medical Research Foundation Inc., Busselton, Australia.
³⁷ PathWest Laboratory Medicine WA, Nedlands, Western Australia.
³⁸ School of Pathology & Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia.
³⁹ School of Population Health, The University of Western Australia, Nedlands, Western Australia.
⁴⁰ Harokopio University, Athens, Greece.
⁴¹ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, MD, USA.
⁴² Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK.
⁴³ QIMR Berghofer Medical Research Institute, Queensland, Australia.
⁴⁴ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁴⁵ Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
⁴⁶ Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands.
⁴⁷ Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
⁴⁸ Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
⁴⁹ Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
⁵⁰ Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
⁵¹ University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
⁵² Department of Odontology, Umeå University, Umeå, Sweden.
⁵³ Biocenter Oulu, University of Oulu, Oulu, Finland.
⁵⁴ Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, UK.
⁵⁵ Institute for Community Medicine, University Medicine Greifswald, Germany.
⁵⁶ Department of Prosthodontics, Gerodontology and Biomaterials, Center of Oral Health, University Medicine Greifswald, Germany.
⁵⁷ Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
⁵⁸ Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
⁵⁹ Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
⁶⁰ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁶¹ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
⁶² Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
⁶³ Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
⁶⁴ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
⁶⁵ Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
⁶⁶ Department of Clinical Physiology, Tampere University Hospital and School of Medicine University of Tampere, Tampere, Finland.
⁶⁷ Department of Clinical Chemistry, Fimlab Laboratories, and School of Medicine, University of Tampere, Tampere, Finland.
⁶⁸ Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland.
⁶⁹ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
⁷⁰ Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
⁷¹ Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, USA.
⁷² Department of Health Services, University of Washington, Seattle, Washington, USA.
⁷³ Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.
⁷⁴ Institute of Epidemiology, Helmholtz Zentrum-München, Munich-Neuherberg, Germany.
⁷⁵ Department of Psychiatry, Washington University, St.Louis, Missouri, USA.
⁷⁶ Department for Psychiatry, Johannes-Gutenberg-University, Mainz, Germany.
⁷⁷ School of Applied Sciences, University of Mississippi, Oxford, Mississippi, USA.
⁷⁸ Clinical Laboratory & Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, USA.
⁷⁹ Department of Genomics of Common Diseases, Imperial College London, London, UK.
⁸⁰ Medical Department, University of Leipzig, Germany.
⁸¹ IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.
⁸² William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁸³ King Abdulaziz University, Jeddah, Saudi Arabia.
⁸⁴ Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁸⁵ Center for Non-Communicable Diseases, Pakistan.
⁸⁶ Health Disparities Research Section, Clinical Research Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA.
⁸⁷ Laboratory of Personality and Cognition, National Institute on Aging, NIH, Baltimore, Maryland, USA.
⁸⁸ Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁸⁹ Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁹⁰ Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
⁹¹ Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
⁹² Mass Eye and Ear Infirmary, Boston, Massachusetts, USA.
⁹³ Geriatric Unit, Azienda Sanitaria Firenze, Florence, Italy.
⁹⁴ Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA.
⁹⁵ Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁹⁶ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
⁹⁷ Research Unit of Molecular Epidemiology, Helmholtz Zentrum-München, Munich-Neuherberg, Germany.
⁹⁸ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁹⁹ Department of General Practice and Primary health Care, University of Helsinki, Helsinki, Finland.
¹⁰⁰ Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.
¹⁰¹ Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, USA.
¹⁰² The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁰³ The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁰⁴ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS Hospital Stralsund, Germany.
¹⁰⁵ Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
¹⁰⁶ Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁰⁷ School of Population Health, University of South Australia, Adelaide, Australia.
¹⁰⁸ South Australian Health and Medical Research Institute, Adelaide, Australia.
¹⁰⁹ Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland.
¹¹⁰ Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
¹¹¹ The Framingham Heart Study, Framingham, Massachusetts, USA.
¹¹² Department of Public Health & Clinical Medicine, Section for Medicine, Umeå University, Umeå, Sweden.
¹¹³ Netherlands Consortium for Healthy Ageing and National Genomics Initiative, Leiden, The Netherlands.
¹¹⁴ Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, Texas, USA.
¹¹⁵ 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.

^# Contributed equally.

PMID: 25288136
PMCID: PMC4388784
DOI: 10.1038/mp.2014.107

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.

PubMed Disclaimer

Figures

**Figure 1**
Network describing direct interactions between candidate genes of confirmed loci. Relationships were retrieved from databases of transcription regulation and protein-protein interaction experiments (Supplementary Table S21). Genes are represented as nodes that are colored according to locus. Candidate genes for loci identified in the current study were supplemented with known candidate genes related to caffeine pharmacology (grey nodes). Edges indicate known interactions.

See this image and copyright information in PMC

Comment in

Connecting the dots, genome-wide association studies in substance use.
Nivard MG, Verweij KJ, Minică CC, Treur JL; International Cannabis Consortium; Vink JM, Boomsma DI. Nivard MG, et al. Mol Psychiatry. 2016 Jun;21(6):733-5. doi: 10.1038/mp.2016.14. Epub 2016 Mar 15. Mol Psychiatry. 2016. PMID: 26976040 No abstract available.

References

1. Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999;51(1):83–133. - PubMed
1. Cornelis M. Gene-coffee interactions and health. Curr Nutr Rep. 2014 in press.
1. Spiller MA. The chemical components of coffee. In: Spiller GA, editor. Caffeine. CRC; Boca Raton: 1998. pp. 97–161.
1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 5 edn. Arlington, VA; American Psychiatric Publishing: 2013.
1. Cornelis MC. Coffee intake. Progress in molecular biology and translational science. 2012;108:293–322. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Figures

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Miscellaneous