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

M. C. Cornelis, E. M. Byrne, T. Esko, M. A. Nalls, A. Ganna, N. Paynter, K. L. Monda, N. Amin, K. Fischer, F. Renstrom, J. S. Ngwa, V. Huikari, A. Cavadino, I. M. Nolte, A. Teumer, K. Yu, P. Marques-Vidal, R. Rawal, A. Manichaikul, M. K. WojczynskiJ. M. Vink, J. H. Zhao, G. Burlutsky, J. Lahti, V. Mikkilä, R. N. Lemaitre, J. Eriksson, S. K. Musani, T. Tanaka, F. Geller, J. Luan, J. Hui, R. Mägi, M. Dimitriou, M. E. Garcia, W. K. Ho, M. J. Wright, L. M. Rose, P. K.E. Magnusson, N. L. Pedersen, D. Couper, B. A. Oostra, A. Hofman, M. A. Ikram, H. W. Tiemeier, A. G. Uitterlinden, F. J.A. van Rooij, I. Barroso, I. Johansson, L. Xue, M. Kaakinen, L. Milani, C. Power, H. Snieder, R. P. Stolk, S. E. Baumeister, R. Biffar, F. Gu, F. Bastardot, Z. Kutalik, D. R. Jacobs, N. G. Forouhi, E. Mihailov, L. Lind, C. Lindgren, K. Michaëlsson, A. Morris, M. Jensen, K. T. Khaw, R. N. Luben, J. J. Wang, S. Männistö, M. M. Perälä, M. Kähönen, T. Lehtimäki, J. Viikari, D. Mozaffarian, K. Mukamal, B. M. Psaty, A. Döring, A. C. Heath, G. W. Montgomery, N. Dahmen, T. Carithers, K. L. Tucker, L. Ferrucci, H. A. Boyd, M. Melbye, J. L. Treur, D. Mellström, J. J. Hottenga, I. Prokopenko, A. Tönjes, P. Deloukas, S. Kanoni, M. Lorentzon, D. K. Houston, Y. Liu, J. Danesh, A. Rasheed, M. A. Mason, A. B. Zonderman, L. Franke, B. S. Kristal, J. Karjalainen, D. R. Reed, H. J. Westra, M. K. Evans, D. Saleheen, T. B. Harris, G. Dedoussis, G. Curhan, M. Stumvoll, J. Beilby, L. R. Pasquale, B. Feenstra, S. Bandinelli, J. M. Ordovas, A. T. Chan, U. Peters, C. Ohlsson, C. Gieger, N. G. Martin, M. Waldenberger, D. S. Siscovick, O. Raitakari, J. G. Eriksson, P. Mitchell, D. J. Hunter, P. Kraft, E. B. Rimm, D. I. Boomsma, I. B. Borecki, R. J.F. Loos, N. J. Wareham, P. Vollenweider, N. Caporaso, H. J. Grabe, M. L. Neuhouser, B. H.R. Wolffenbuttel, F. B. Hu, E. Hyppönen, M. R. Järvelin, L. A. Cupples, P. W. Franks, P. M. Ridker, C. M. van Duijn, G. Heiss, A. Metspalu, K. E. North, E. Ingelsson, J. A. Nettleton, R. M. van Dam, D. I. Chasman, 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, Jose 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, Isabel Wurster, Walter Mätzler, Gavin Hudson, Sarah E. Hunt, Johanna Huttenlocher, Thomas Illig, Pálmi V. Jónsson, Jean Charles Lambert, Cordelia Langford, Andrew Lees, Peter Lichtner, Patricia Limousin, Grisel Lopez, Delia Lorenz, Alisdair McNeill, Catriona Moorby, Matthew Moore, Huw R. Morris, Karen E. Morrison, Ese Mudanohwo, Sean S. O’sullivan, Justin Pearson, Joel S. Perlmutter, Hjörvar Pétursson, Pierre Pollak, Bart Post, Simon Potter, Bernard Ravina, Tamas Revesz, Olaf Riess, Fernando Rivadeneira, Patrizia Rizzu, Mina Ryten, Stephen Sawcer, Anthony Schapira, Hans Scheffer, Karen Shaw, Ira Shoulson, Ellen Sidransky, Colin Smith, Chris C.A. Spencer, Hreinn Stefánsson, Francesco Bettella, Joanna D. Stockton, Amy Strange, Kevin Talbot, Carlie 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, Nicholas W. Wood, John Hardy, Peter Heutink, Alexis Brice, Thomas Gasser, Andrew B. Singleton, Andrew Singleton, Mark Cookson, J. Raphael Gibbs, Reta Lila, Dena Hernandez, Reta Lila, 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, Reta Lila, Daniah Trabzuni, Colin Smith, Robert Walker

Research output: Contribution to journalComment/debate

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 (log 10 Bayes 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.

Original languageEnglish (US)
Pages (from-to)647-656
Number of pages10
JournalMolecular psychiatry
Volume20
Issue number5
DOIs
StatePublished - May 30 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Cornelis, M. C., Byrne, E. M., Esko, T., Nalls, M. A., Ganna, A., Paynter, N., Monda, K. L., Amin, N., Fischer, K., Renstrom, F., Ngwa, J. S., Huikari, V., Cavadino, A., Nolte, I. M., Teumer, A., Yu, K., Marques-Vidal, P., Rawal, R., Manichaikul, A., ... Walker, R. (2015). Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Molecular psychiatry, 20(5), 647-656. https://doi.org/10.1038/mp.2014.107