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. Wojczynski; J. 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 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; 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; Reta Lila; Dena Hernandez; Reta Lila; Allissa Dillman; Michael Nalls; Alan Zonderman; Sampath Arepalli; Robert Johnson; Dan Longo; Richard O'brien; Bryan Traynor; Juan Troncoso; Marcel van der Brug; Ronald Zielke; Michael Weale; Mina Ryten; Adaikalavan Ramasamy; Reta Lila; Daniah Trabzuni; Robert Walker

doi:10.1038/mp.2014.107

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. Wojczynski

J. 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 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, 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, Reta Lila, Dena Hernandez, Reta Lila, Allissa Dillman, Michael Nalls, Alan Zonderman, Sampath Arepalli, Robert Johnson, Dan Longo, Richard O'brien, Bryan Traynor, Juan Troncoso, Marcel van der Brug, Ronald Zielke, Michael Weale, Mina Ryten, Adaikalavan Ramasamy, Reta Lila, Daniah Trabzuni, Robert Walker

^*Corresponding author for this work

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226 Citations (Scopus)

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 language	English
Pages (from-to)	647-656
Number of pages	10
Journal	Molecular Psychiatry
Volume	20
Issue number	5
DOIs	https://doi.org/10.1038/mp.2014.107
Publication status	Published - 30 May 2015
Externally published	Yes

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10.1038/mp.2014.107

Cite this

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

@article{39573f12eaa54a9d8e87fff7c50d2b5a,

title = "Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption",

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.",

author = "Cornelis, \{M. C.\} and Byrne, \{E. M.\} and T. Esko and Nalls, \{M. A.\} and A. Ganna and N. Paynter and Monda, \{K. L.\} and N. Amin and K. Fischer and F. Renstrom and Ngwa, \{J. S.\} and V. Huikari and A. Cavadino and Nolte, \{I. M.\} and A. Teumer and K. Yu and P. Marques-Vidal and R. Rawal and A. Manichaikul and Wojczynski, \{M. K.\} and Vink, \{J. M.\} and Zhao, \{J. H.\} and G. Burlutsky and J. Lahti and V. Mikkil{\"a} and Lemaitre, \{R. N.\} and J. Eriksson and Musani, \{S. K.\} and T. Tanaka and F. Geller and J. Luan and J. Hui and R. M{\"a}gi and M. Dimitriou and Garcia, \{M. E.\} and Ho, \{W. K.\} and Wright, \{M. J.\} and Rose, \{L. M.\} and Magnusson, \{P. K.E.\} and Pedersen, \{N. L.\} and D. Couper and Oostra, \{B. A.\} and A. Hofman and Ikram, \{M. A.\} and Tiemeier, \{H. W.\} and Uitterlinden, \{A. G.\} and \{van Rooij\}, \{F. J.A.\} and I. Barroso and I. Johansson and L. Xue and M. Kaakinen and L. Milani and C. Power and H. Snieder and Stolk, \{R. P.\} and Baumeister, \{S. E.\} and R. Biffar and F. Gu and F. Bastardot and Z. Kutalik and Jacobs, \{D. R.\} and Forouhi, \{N. G.\} and E. Mihailov and L. Lind and C. Lindgren and K. Micha{\"e}lsson and A. Morris and M. Jensen and Khaw, \{K. T.\} and Luben, \{R. N.\} and Wang, \{J. J.\} and S. M{\"a}nnist{\"o} and Per{\"a}l{\"a}, \{M. M.\} and M. K{\"a}h{\"o}nen and T. Lehtim{\"a}ki and J. Viikari and D. Mozaffarian and K. Mukamal and Psaty, \{B. M.\} and A. D{\"o}ring and Heath, \{A. C.\} and Montgomery, \{G. W.\} and N. Dahmen and T. Carithers and Tucker, \{K. L.\} and L. Ferrucci and Boyd, \{H. A.\} and M. Melbye and Treur, \{J. L.\} and D. Mellstr{\"o}m and Hottenga, \{J. J.\} and I. Prokopenko and A. T{\"o}njes and P. Deloukas and S. Kanoni and M. Lorentzon and Houston, \{D. K.\} and Y. Liu and J. Danesh and A. Rasheed and Mason, \{M. A.\} and Zonderman, \{A. B.\} and L. Franke and Kristal, \{B. S.\} and J. Karjalainen and Reed, \{D. R.\} and Westra, \{H. J.\} and Evans, \{M. K.\} and D. Saleheen and Harris, \{T. B.\} and G. Dedoussis and G. Curhan and M. Stumvoll and J. Beilby and Pasquale, \{L. R.\} and B. Feenstra and S. Bandinelli and Ordovas, \{J. M.\} and Chan, \{A. T.\} and U. Peters and C. Ohlsson and C. Gieger and Martin, \{N. G.\} and M. Waldenberger and Siscovick, \{D. S.\} and O. Raitakari and Eriksson, \{J. G.\} and P. Mitchell and Hunter, \{D. J.\} and P. Kraft and Rimm, \{E. B.\} and Boomsma, \{D. I.\} and Borecki, \{I. B.\} and Loos, \{R. J.F.\} and Wareham, \{N. J.\} and P. Vollenweider and N. Caporaso and Grabe, \{H. J.\} and Neuhouser, \{M. L.\} and Wolffenbuttel, \{B. H.R.\} and Hu, \{F. B.\} and E. Hypp{\"o}nen and J{\"a}rvelin, \{M. R.\} and Cupples, \{L. A.\} and Franks, \{P. W.\} and Ridker, \{P. M.\} and \{van Duijn\}, \{C. M.\} and G. Heiss and A. Metspalu and North, \{K. E.\} and E. Ingelsson and Nettleton, \{J. A.\} and \{van Dam\}, \{R. M.\} and Chasman, \{D. I.\} and Nalls, \{Michael A.\} and Vincent Plagnol and Hernandez, \{Dena G.\} and Manu Sharma and Sheerin, \{Una Marie\} and Mohamad Saad and Javier Sim{\'o}n-S{\'a}nchez and Claudia Schulte and Suzanne Lesage and Sigurlaug Sveinbj{\"o}rnsd{\'o}ttir and Sampath Arepalli and Roger Barker and Yoav Ben-Shlomo and Berendse, \{Henk W.\} and Daniela Berg and Kailash Bhatia and \{de Bie\}, \{Rob M.A.\} and Alessandro Biffi and Bas Bloem and Zoltan Bochdanovits and Michael Bonin and Bras, \{Jose M.\} and Kathrin Brockmann and Janet Brooks and Burn, \{David J.\} and Gavin Charlesworth and Honglei Chen and Chinnery, \{Patrick F.\} and Sean Chong and Clarke, \{Carl E.\} and Cookson, \{Mark R.\} and Cooper, \{J. Mark\} and Corvol, \{Jean Christophe\} and Carl Counsell and Philippe Damier and Dartigues, \{Jean Fran{\c c}ois\} and Panos Deloukas and G{\"u}nther Deuschl and Dexter, \{David T.\} and Dijk, \{Karin D.van\} and Allissa Dillman and Frank Durif and Alexandra D{\"u}rr and Sarah Edkins and Evans, \{Jonathan R.\} and Thomas Foltynie and Jing Dong and Michelle Gardner and Gibbs, \{J. Raphael\} and Alison Goate and Emma Gray and Rita Guerreiro and Clare Harris and Hilten, \{Jacobus J.van\} and Albert Hollenbeck and Janice Holton and Michele Hu and Xuemei Huang and Isabel Wurster and Walter M{\"a}tzler and Gavin Hudson and Hunt, \{Sarah E.\} and Johanna Huttenlocher and Thomas Illig and J{\'o}nsson, \{P{\'a}lmi V.\} and Lambert, \{Jean Charles\} and Cordelia Langford and Andrew Lees and Peter Lichtner and Patricia Limousin and Grisel Lopez and Delia Lorenz and Alisdair McNeill and Catriona Moorby and Matthew Moore and Morris, \{Huw R.\} and Morrison, \{Karen E.\} and Ese Mudanohwo and O{\textquoteright}sullivan, \{Sean S.\} and Justin Pearson and Perlmutter, \{Joel S.\} and Hj{\"o}rvar P{\'e}tursson and Pierre Pollak and Bart Post and Simon Potter and Bernard Ravina and Tamas Revesz and Olaf Riess and Fernando Rivadeneira and Patrizia Rizzu and Mina Ryten and Stephen Sawcer and Anthony Schapira and Hans Scheffer and Karen Shaw and Ira Shoulson and Ellen Sidransky and Colin Smith and Spencer, \{Chris C.A.\} and Hreinn Stef{\'a}nsson and Francesco Bettella and Stockton, \{Joanna D.\} and Amy Strange and Kevin Talbot and Tanner, \{Carlie M.\} and Avazeh Tashakkori-Ghanbaria and Fran{\c c}ois Tison and Daniah Trabzuni and Traynor, \{Bryan J.\} and Daan Velseboer and Marie Vidailhet and Robert Walker and Warrenburg, \{Bart van de\} and Mirdhu Wickremaratchi and Nigel Williams and Williams-Gray, \{Caroline H.\} and Sophie Winder-Rhodes and K{\'a}ri Stef{\'a}nsson and Maria Martinez and Wood, \{Nicholas W.\} and John Hardy and Peter Heutink and Alexis Brice and Thomas Gasser and Singleton, \{Andrew B.\} and Andrew Singleton and Mark Cookson and Reta Lila and Dena Hernandez and Reta Lila and Allissa Dillman and Michael Nalls and Alan Zonderman and Sampath Arepalli and Robert Johnson and Dan Longo and Richard O'brien and Bryan Traynor and Juan Troncoso and Brug, \{Marcel van der\} and Ronald Zielke and Michael Weale and Mina Ryten and Adaikalavan Ramasamy and Reta Lila and Daniah Trabzuni and Robert Walker",

note = "Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

year = "2015",

month = may,

day = "30",

doi = "10.1038/mp.2014.107",

language = "English",

volume = "20",

pages = "647--656",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer Nature",

number = "5",

}

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, 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, PKE, Pedersen, NL, Couper, D, Oostra, BA, Hofman, A, Ikram, MA, Tiemeier, HW, Uitterlinden, AG, van Rooij, FJA, 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, 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, RJF, Wareham, NJ, Vollenweider, P, Caporaso, N, Grabe, HJ, Neuhouser, ML, Wolffenbuttel, BHR, 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, 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, RMA, Biffi, A, Bloem, B, Bochdanovits, Z, Bonin, M, Bras, JM, 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, Dijk, KDV, 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, Hilten, JJV, Hollenbeck, A, Holton, J, Hu, M, Huang, X, Wurster, I, Mätzler, W, Hudson, G, Hunt, SE, Huttenlocher, J, Illig, T, Jónsson, PV, Lambert, JC, Langford, C, Lees, A, Lichtner, P, Limousin, P, Lopez, G, Lorenz, D, McNeill, A, Moorby, C, Moore, M, Morris, HR, Morrison, KE, Mudanohwo, E, O’sullivan, SS, Pearson, J, Perlmutter, JS, Pétursson, H, Pollak, P, Post, B, Potter, S, Ravina, B, Revesz, T, Riess, O, Rivadeneira, F, Rizzu, P, Ryten, M, Sawcer, S, Schapira, A, Scheffer, H, Shaw, K, Shoulson, I, Sidransky, E, Smith, C, Spencer, CCA, Stefánsson, H, Bettella, F, Stockton, JD, Strange, A, Talbot, K, Tanner, CM, Tashakkori-Ghanbaria, A, Tison, F, Trabzuni, D, Traynor, BJ, Velseboer, D, Vidailhet, M, Walker, R, Warrenburg, BVD, Wickremaratchi, M, Williams, N, Williams-Gray, CH, Winder-Rhodes, S, Stefánsson, K, Martinez, M, Wood, NW, Hardy, J, Heutink, P, Brice, A, Gasser, T, Singleton, AB, Singleton, A, Cookson, M, Lila, R, Hernandez, D, Lila, R, Dillman, A, Nalls, M, Zonderman, A, Arepalli, S, Johnson, R, Longo, D, O'brien, R, Traynor, B, Troncoso, J, Brug, MVD, Zielke, R, Weale, M, Ryten, M, Ramasamy, A, Lila, R, Trabzuni, D & Walker, R 2015, 'Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption', Molecular Psychiatry, vol. 20, no. 5, pp. 647-656. https://doi.org/10.1038/mp.2014.107

TY - JOUR

T1 - Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

AU - Cornelis, M. C.

AU - Byrne, E. M.

AU - Esko, T.

AU - Nalls, M. A.

AU - Ganna, A.

AU - Paynter, N.

AU - Monda, K. L.

AU - Amin, N.

AU - Fischer, K.

AU - Renstrom, F.

AU - Ngwa, J. S.

AU - Huikari, V.

AU - Cavadino, A.

AU - Nolte, I. M.

AU - Teumer, A.

AU - Yu, K.

AU - Marques-Vidal, P.

AU - Rawal, R.

AU - Manichaikul, A.

AU - Wojczynski, M. K.

AU - Vink, J. M.

AU - Zhao, J. H.

AU - Burlutsky, G.

AU - Lahti, J.

AU - Mikkilä, V.

AU - Lemaitre, R. N.

AU - Eriksson, J.

AU - Musani, S. K.

AU - Tanaka, T.

AU - Geller, F.

AU - Luan, J.

AU - Hui, J.

AU - Mägi, R.

AU - Dimitriou, M.

AU - Garcia, M. E.

AU - Ho, W. K.

AU - Wright, M. J.

AU - Rose, L. M.

AU - Magnusson, P. K.E.

AU - Pedersen, N. L.

AU - Couper, D.

AU - Oostra, B. A.

AU - Hofman, A.

AU - Ikram, M. A.

AU - Tiemeier, H. W.

AU - Uitterlinden, A. G.

AU - van Rooij, F. J.A.

AU - Barroso, I.

AU - Johansson, I.

AU - Xue, L.

AU - Kaakinen, M.

AU - Milani, L.

AU - Power, C.

AU - Snieder, H.

AU - Stolk, R. P.

AU - Baumeister, S. E.

AU - Biffar, R.

AU - Gu, F.

AU - Bastardot, F.

AU - Kutalik, Z.

AU - Jacobs, D. R.

AU - Forouhi, N. G.

AU - Mihailov, E.

AU - Lind, L.

AU - Lindgren, C.

AU - Michaëlsson, K.

AU - Morris, A.

AU - Jensen, M.

AU - Khaw, K. T.

AU - Luben, R. N.

AU - Wang, J. J.

AU - Männistö, S.

AU - Perälä, M. M.

AU - Kähönen, M.

AU - Lehtimäki, T.

AU - Viikari, J.

AU - Mozaffarian, D.

AU - Mukamal, K.

AU - Psaty, B. M.

AU - Döring, A.

AU - Heath, A. C.

AU - Montgomery, G. W.

AU - Dahmen, N.

AU - Carithers, T.

AU - Tucker, K. L.

AU - Ferrucci, L.

AU - Boyd, H. A.

AU - Melbye, M.

AU - Treur, J. L.

AU - Mellström, D.

AU - Hottenga, J. J.

AU - Prokopenko, I.

AU - Tönjes, A.

AU - Deloukas, P.

AU - Kanoni, S.

AU - Lorentzon, M.

AU - Houston, D. K.

AU - Liu, Y.

AU - Danesh, J.

AU - Rasheed, A.

AU - Mason, M. A.

AU - Zonderman, A. B.

AU - Franke, L.

AU - Kristal, B. S.

AU - Karjalainen, J.

AU - Reed, D. R.

AU - Westra, H. J.

AU - Evans, M. K.

AU - Saleheen, D.

AU - Harris, T. B.

AU - Dedoussis, G.

AU - Curhan, G.

AU - Stumvoll, M.

AU - Beilby, J.

AU - Pasquale, L. R.

AU - Feenstra, B.

AU - Bandinelli, S.

AU - Ordovas, J. M.

AU - Chan, A. T.

AU - Peters, U.

AU - Ohlsson, C.

AU - Gieger, C.

AU - Martin, N. G.

AU - Waldenberger, M.

AU - Siscovick, D. S.

AU - Raitakari, O.

AU - Eriksson, J. G.

AU - Mitchell, P.

AU - Hunter, D. J.

AU - Kraft, P.

AU - Rimm, E. B.

AU - Boomsma, D. I.

AU - Borecki, I. B.

AU - Loos, R. J.F.

AU - Wareham, N. J.

AU - Vollenweider, P.

AU - Caporaso, N.

AU - Grabe, H. J.

AU - Neuhouser, M. L.

AU - Wolffenbuttel, B. H.R.

AU - Hu, F. B.

AU - Hyppönen, E.

AU - Järvelin, M. R.

AU - Cupples, L. A.

AU - Franks, P. W.

AU - Ridker, P. M.

AU - van Duijn, C. M.

AU - Heiss, G.

AU - Metspalu, A.

AU - North, K. E.

AU - Ingelsson, E.

AU - Nettleton, J. A.

AU - van Dam, R. M.

AU - Chasman, D. I.

AU - Nalls, Michael A.

AU - Plagnol, Vincent

AU - Hernandez, Dena G.

AU - Sharma, Manu

AU - Sheerin, Una Marie

AU - Saad, Mohamad

AU - Simón-Sánchez, Javier

AU - Schulte, Claudia

AU - Lesage, Suzanne

AU - Sveinbjörnsdóttir, Sigurlaug

AU - Arepalli, Sampath

AU - Barker, Roger

AU - Ben-Shlomo, Yoav

AU - Berendse, Henk W.

AU - Berg, Daniela

AU - Bhatia, Kailash

AU - de Bie, Rob M.A.

AU - Biffi, Alessandro

AU - Bloem, Bas

AU - Bochdanovits, Zoltan

AU - Bonin, Michael

AU - Bras, Jose M.

AU - Brockmann, Kathrin

AU - Brooks, Janet

AU - Burn, David J.

AU - Charlesworth, Gavin

AU - Chen, Honglei

AU - Chinnery, Patrick F.

AU - Chong, Sean

AU - Clarke, Carl E.

AU - Cookson, Mark R.

AU - Cooper, J. Mark

AU - Corvol, Jean Christophe

AU - Counsell, Carl

AU - Damier, Philippe

AU - Dartigues, Jean François

AU - Deloukas, Panos

AU - Deuschl, Günther

AU - Dexter, David T.

AU - Dijk, Karin D.van

AU - Dillman, Allissa

AU - Durif, Frank

AU - Dürr, Alexandra

AU - Edkins, Sarah

AU - Evans, Jonathan R.

AU - Foltynie, Thomas

AU - Dong, Jing

AU - Gardner, Michelle

AU - Gibbs, J. Raphael

AU - Goate, Alison

AU - Gray, Emma

AU - Guerreiro, Rita

AU - Harris, Clare

AU - Hilten, Jacobus J.van

AU - Hollenbeck, Albert

AU - Holton, Janice

AU - Hu, Michele

AU - Huang, Xuemei

AU - Wurster, Isabel

AU - Mätzler, Walter

AU - Hudson, Gavin

AU - Hunt, Sarah E.

AU - Huttenlocher, Johanna

AU - Illig, Thomas

AU - Jónsson, Pálmi V.

AU - Lambert, Jean Charles

AU - Langford, Cordelia

AU - Lees, Andrew

AU - Lichtner, Peter

AU - Limousin, Patricia

AU - Lopez, Grisel

AU - Lorenz, Delia

AU - McNeill, Alisdair

AU - Moorby, Catriona

AU - Moore, Matthew

AU - Morris, Huw R.

AU - Morrison, Karen E.

AU - Mudanohwo, Ese

AU - O’sullivan, Sean S.

AU - Pearson, Justin

AU - Perlmutter, Joel S.

AU - Pétursson, Hjörvar

AU - Pollak, Pierre

AU - Post, Bart

AU - Potter, Simon

AU - Ravina, Bernard

AU - Revesz, Tamas

AU - Riess, Olaf

AU - Rivadeneira, Fernando

AU - Rizzu, Patrizia

AU - Ryten, Mina

AU - Sawcer, Stephen

AU - Schapira, Anthony

AU - Scheffer, Hans

AU - Shaw, Karen

AU - Shoulson, Ira

AU - Sidransky, Ellen

AU - Smith, Colin

AU - Spencer, Chris C.A.

AU - Stefánsson, Hreinn

AU - Bettella, Francesco

AU - Stockton, Joanna D.

AU - Strange, Amy

AU - Talbot, Kevin

AU - Tanner, Carlie M.

AU - Tashakkori-Ghanbaria, Avazeh

AU - Tison, François

AU - Trabzuni, Daniah

AU - Traynor, Bryan J.

AU - Velseboer, Daan

AU - Vidailhet, Marie

AU - Walker, Robert

AU - Warrenburg, Bart van de

AU - Wickremaratchi, Mirdhu

AU - Williams, Nigel

AU - Williams-Gray, Caroline H.

AU - Winder-Rhodes, Sophie

AU - Stefánsson, Kári

AU - Martinez, Maria

AU - Wood, Nicholas W.

AU - Hardy, John

AU - Heutink, Peter

AU - Brice, Alexis

AU - Gasser, Thomas

AU - Singleton, Andrew B.

AU - Singleton, Andrew

AU - Cookson, Mark

AU - Lila, Reta

AU - Hernandez, Dena

AU - Lila, Reta

AU - Dillman, Allissa

AU - Nalls, Michael

AU - Zonderman, Alan

AU - Arepalli, Sampath

AU - Johnson, Robert

AU - Longo, Dan

AU - O'brien, Richard

AU - Traynor, Bryan

AU - Troncoso, Juan

AU - Brug, Marcel van der

AU - Zielke, Ronald

AU - Weale, Michael

AU - Ryten, Mina

AU - Ramasamy, Adaikalavan

AU - Lila, Reta

AU - Trabzuni, Daniah

AU - Walker, Robert

PY - 2015/5/30

Y1 - 2015/5/30

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84929128366

U2 - 10.1038/mp.2014.107

DO - 10.1038/mp.2014.107

M3 - Comment/debate

C2 - 25288136

AN - SCOPUS:84929128366

SN - 1359-4184

VL - 20

SP - 647

EP - 656

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 5

ER -

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

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