Format

Send to

Choose Destination
Mol Psychiatry. 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, Cornelis MC1,2, Byrne EM#3, Esko T#4,5,6,7, Nalls MA#8, Ganna A9, Paynter N10, Monda KL11, Amin N12, Fischer K4, Renstrom F13, Ngwa JS14, Huikari V15, Cavadino A16, Nolte IM17, Teumer A18, Yu K19, Marques-Vidal P20, Rawal R21, Manichaikul A22, Wojczynski MK23, Vink JM24, Zhao JH25, Burlutsky G26, Lahti J27,28, Mikkilä V29,30, Lemaitre RN31, Eriksson J32, Musani SK33, Tanaka T34, Geller F35, Luan J25, Hui J36,37,38,39, Mägi R4, Dimitriou M40, Garcia ME41, Ho WK42, Wright MJ43, Rose LM10, Magnusson PK9, Pedersen NL9, Couper D44, Oostra BA45, Hofman A12, Ikram MA12,46,47, Tiemeier HW12,48, Uitterlinden AG12,49, van Rooij FJ12, Barroso I50,51, Johansson I52, Xue L14, Kaakinen M15,53,54, Milani L4, Power C16, Snieder H17, Stolk RP17, Baumeister SE55, Biffar R56, Gu F19, Bastardot F57, Kutalik Z58,59,60, Jacobs DR Jr61, Forouhi NG25, Mihailov E4, Lind L62, Lindgren C63, Michaëlsson K64, Morris A63, Jensen M2, Khaw KT42, Luben RN42, Wang JJ26, Männistö S65, Perälä MM65, Kähönen M66, Lehtimäki T67, Viikari J68, Mozaffarian D1,2,69, Mukamal K70, Psaty BM31,71,72,73, Döring A74, Heath AC75, Montgomery GW43, Dahmen N76, Carithers T77, Tucker KL78, Ferrucci L34, Boyd HA35, Melbye M35, Treur JL24, Mellström D32, Hottenga JJ24, Prokopenko I63,79, Tönjes A80,81, Deloukas P50,82,83, Kanoni S82, Lorentzon M32, Houston DK84, Liu Y84, Danesh J42, Rasheed A85, Mason MA86, Zonderman AB87, Franke L88, Kristal BS89,90; International Parkinson’s Disease Genomics Consortium (IPDGC); North American Brain Expression Consortium (NABEC); UK Brain Expression Consortium (UKBEC), Karjalainen J88, Reed DR91, Westra HJ88, Evans MK86, Saleheen D42,85, Harris TB41, Dedoussis G40, Curhan G1, Stumvoll M80,81, Beilby J36,37,38, Pasquale LR1,92, Feenstra B35, Bandinelli S93, Ordovas JM94, Chan AT1,95, Peters U96, Ohlsson C32, Gieger C21, Martin NG43, Waldenberger M97, Siscovick DS31,71, Raitakari O30,98, Eriksson JG28,99,100, Mitchell P26, Hunter DJ1,101, Kraft P101, Rimm EB1,2,69, Boomsma DI24, Borecki IB23, Loos RJ25,102,103, Wareham NJ25, Vollenweider P57, Caporaso N19, Grabe HJ104, Neuhouser ML105, Wolffenbuttel BH106, Hu FB1,2,69, Hyppönen E16,107,108, Järvelin MR15,53,54,109,110, Cupples LA14,111, Franks PW2,13,112, Ridker PM10, van Duijn CM12,113, Heiss G11, Metspalu A4, North KE11, Ingelsson E62,63, Nettleton JA114, van Dam RM115, Chasman DI10.

Collaborators (152)

Nalls MA, Plagnol V, Hernandez DG, Sharma M, Sheerin UM, Saad M, Simón-Sánchez J, Schulte C, Lesage S, Sveinbjörnsdóttir S, Arepalli S, Barker R, Ben-Shlomo Y, Berendse HW, Berg D, Bhatia K, de Bie RM, Biffi A, Bloem B, Bochdanovits Z, Bonin M, Bras M, Brockmann K, Brooks J, Burn DJ, Charlesworth G, Chen H, Chinnery PF, Chong S, Clarke CE, Cookson MR, Cooper JM, Corvol JC, Counsell C, Damier P, Dartigues JF, Deloukas P, Deuschl G, Dexter DT, van Dijk KD, Dillman A, Durif F, Dürr A, Edkins S, Evans JR, Foltynie T, Dong J, Gardner M, Gibbs JR, Goate A, Gray E, Guerreiro R, Harris C, van Hilten JJ, Hofman A, Hollenbeck A, Holton J, Hu M, Huang X, Hershey MS, Wurster I, Mätzler W, Hudson G, Hunt SE, Huttenlocher J, Illig T, München HZ, Jónsson PV, Lambert JC, Langford C, Lees A, Lichtner P, München HZ, Limousin P, Lopez G, Lorenz D, McNeill A, Moorby C, Moore M, Morris HR, Morrison KE, O' Sullivan SS, Pearson J, Perlmutter JS, Pétursson H, Pollak P, Potter S, Ravina B, Revesz T, Riess O, Rivadeneira F, Rizzu P, Ryten M, Sawcer S, Schapira A, Scheffer H, Shaw K, Sidransky E, Smith C, Spencer CC, Stefánsson H, Bettella F, Stockton JD, Strange A, Talbot K, Tanner M, Tashakkori-Ghanbaria A, Tison F, Trabzuni D, Traynor BJ, Uitterlinden AG, Velseboer D, Vidailhet M, Walker R, van de Warrenburg B, Wickremaratchi M, Williams N, Williams-Gray CH, Winder-Rhodes S, Stefánsson K, Martinez M, Sabatier P, Wood NW, Hardy J, Heutink P, Brice A, Gasser T, Singleton AB, Singleton A, Cookson M, Gibbs J, Hernandez D, Dillman A, Nalls M, Zonderman A, Arepalli S, Ferrucci L, Johnson R, Longo D, O'Brien R, Traynor B, Troncoso J, van der Brug M, Zielke R, Hardy J, Weale M, Ryten M, Ramasamy A, Trabzuni D, Box PO, Smith C, Walker R.

Author information

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

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.

PMID:
25288136
PMCID:
PMC4388784
DOI:
10.1038/mp.2014.107
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center