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, Juan C Troncoso

Research output: Contribution to journalArticle

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

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

Fingerprint

Coffee
Meta-Analysis
Genome
Single Nucleotide Polymorphism
Cytochrome P-450 CYP1A2
Brain-Derived Neurotrophic Factor
Caffeine
Histone Code
Alleles
Beverages
Adiposity
Insurance Benefits
African Americans
Genes
Fasting
Pharmacokinetics
Smoking
Insulin
Blood Pressure
Lipids

ASJC Scopus subject areas

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

Cite this

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. / 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.; Wojczynski, M. K.; Vink, J. M.; Zhao, J. H.; Burlutsky, G.; Lahti, J.; Mikkilä, V.; Lemaitre, R. N.; Eriksson, J.; Musani, S. K.; Tanaka, T.; Geller, F.; Luan, J.; Hui, J.; Mägi, R.; Dimitriou, M.; Garcia, M. E.; Ho, W. K.; Wright, M. J.; Rose, L. M.; Magnusson, P. K E; Pedersen, N. L.; Couper, D.; Oostra, B. A.; Hofman, A.; Ikram, M. A.; Tiemeier, H. W.; Uitterlinden, A. G.; Van Rooij, F. J A; Barroso, I.; Johansson, I.; Xue, L.; Kaakinen, M.; Milani, L.; Power, C.; Snieder, H.; Stolk, R. P.; Baumeister, S. E.; Biffar, R.; Gu, F.; Bastardot, F.; Kutalik, Z.; Jacobs, D. R.; Forouhi, N. G.; Mihailov, E.; Lind, L.; Lindgren, C.; Michaëlsson, K.; Morris, A.; Jensen, M.; Khaw, K. T.; Luben, R. N.; Wang, J. J.; Männistö, S.; Perälä, M. M.; Kähönen, M.; Lehtimäki, T.; Viikari, J.; Mozaffarian, D.; Mukamal, K.; Psaty, B. M.; Döring, A.; Heath, A. C.; Montgomery, G. W.; Dahmen, N.; Carithers, T.; Tucker, K. L.; Ferrucci, L.; Boyd, H. A.; Melbye, M.; Treur, J. L.; Mellström, D.; Hottenga, J. J.; Prokopenko, I.; Tönjes, A.; Deloukas, P.; Kanoni, S.; Lorentzon, M.; Houston, D. K.; Liu, Y.; Danesh, J.; Rasheed, A.; Mason, M. A.; Zonderman, A. B.; Franke, L.; Kristal, B. S.; Karjalainen, J.; Reed, D. R.; Westra, H. J.; Evans, M. K.; Saleheen, D.; Harris, T. B.; Dedoussis, G.; Curhan, G.; Stumvoll, M.; Beilby, J.; Pasquale, L. R.; Feenstra, B.; Bandinelli, S.; Ordovas, J. M.; Chan, A. T.; Peters, U.; Ohlsson, C.; Gieger, C.; Martin, N. G.; Waldenberger, M.; Siscovick, D. S.; Raitakari, O.; Eriksson, J. G.; Mitchell, P.; Hunter, D. J.; Kraft, P.; Rimm, E. B.; Boomsma, D. I.; Borecki, I. B.; Loos, R. J F; Wareham, N. J.; Vollenweider, P.; Caporaso, N.; Grabe, H. J.; Neuhouser, M. L.; Wolffenbuttel, B. H R; Hu, F. B.; Hyppönen, E.; Järvelin, M. R.; Cupples, L. A.; Franks, P. W.; Ridker, P. M.; Van Duijn, C. M.; Heiss, G.; Metspalu, A.; North, K. E.; Ingelsson, E.; Nettleton, J. A.; Van Dam, R. M.; Troncoso, Juan C.

In: Molecular Psychiatry, Vol. 20, No. 5, 30.05.2015, p. 647-656.

Research output: Contribution to journalArticle

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 & Troncoso, JC 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
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. ; Wojczynski, M. K. ; Vink, J. M. ; Zhao, J. H. ; Burlutsky, G. ; Lahti, J. ; Mikkilä, V. ; Lemaitre, R. N. ; Eriksson, J. ; Musani, S. K. ; Tanaka, T. ; Geller, F. ; Luan, J. ; Hui, J. ; Mägi, R. ; Dimitriou, M. ; Garcia, M. E. ; Ho, W. K. ; Wright, M. J. ; Rose, L. M. ; Magnusson, P. K E ; Pedersen, N. L. ; Couper, D. ; Oostra, B. A. ; Hofman, A. ; Ikram, M. A. ; Tiemeier, H. W. ; Uitterlinden, A. G. ; Van Rooij, F. J A ; Barroso, I. ; Johansson, I. ; Xue, L. ; Kaakinen, M. ; Milani, L. ; Power, C. ; Snieder, H. ; Stolk, R. P. ; Baumeister, S. E. ; Biffar, R. ; Gu, F. ; Bastardot, F. ; Kutalik, Z. ; Jacobs, D. R. ; Forouhi, N. G. ; Mihailov, E. ; Lind, L. ; Lindgren, C. ; Michaëlsson, K. ; Morris, A. ; Jensen, M. ; Khaw, K. T. ; Luben, R. N. ; Wang, J. J. ; Männistö, S. ; Perälä, M. M. ; Kähönen, M. ; Lehtimäki, T. ; Viikari, J. ; Mozaffarian, D. ; Mukamal, K. ; Psaty, B. M. ; Döring, A. ; Heath, A. C. ; Montgomery, G. W. ; Dahmen, N. ; Carithers, T. ; Tucker, K. L. ; Ferrucci, L. ; Boyd, H. A. ; Melbye, M. ; Treur, J. L. ; Mellström, D. ; Hottenga, J. J. ; Prokopenko, I. ; Tönjes, A. ; Deloukas, P. ; Kanoni, S. ; Lorentzon, M. ; Houston, D. K. ; Liu, Y. ; Danesh, J. ; Rasheed, A. ; Mason, M. A. ; Zonderman, A. B. ; Franke, L. ; Kristal, B. S. ; Karjalainen, J. ; Reed, D. R. ; Westra, H. J. ; Evans, M. K. ; Saleheen, D. ; Harris, T. B. ; Dedoussis, G. ; Curhan, G. ; Stumvoll, M. ; Beilby, J. ; Pasquale, L. R. ; Feenstra, B. ; Bandinelli, S. ; Ordovas, J. M. ; Chan, A. T. ; Peters, U. ; Ohlsson, C. ; Gieger, C. ; Martin, N. G. ; Waldenberger, M. ; Siscovick, D. S. ; Raitakari, O. ; Eriksson, J. G. ; Mitchell, P. ; Hunter, D. J. ; Kraft, P. ; Rimm, E. B. ; Boomsma, D. I. ; Borecki, I. B. ; Loos, R. J F ; Wareham, N. J. ; Vollenweider, P. ; Caporaso, N. ; Grabe, H. J. ; Neuhouser, M. L. ; Wolffenbuttel, B. H R ; Hu, F. B. ; Hyppönen, E. ; Järvelin, M. R. ; Cupples, L. A. ; Franks, P. W. ; Ridker, P. M. ; Van Duijn, C. M. ; Heiss, G. ; Metspalu, A. ; North, K. E. ; Ingelsson, E. ; Nettleton, J. A. ; Van Dam, R. M. ; Troncoso, Juan C. / Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. In: Molecular Psychiatry. 2015 ; Vol. 20, No. 5. pp. 647-656.
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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",
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 Troncoso, {Juan C}",
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pages = "647--656",
journal = "Molecular Psychiatry",
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}

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 - Troncoso, Juan C

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

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

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U2 - 10.1038/mp.2014.107

DO - 10.1038/mp.2014.107

M3 - Article

C2 - 25288136

AN - SCOPUS:84929128366

VL - 20

SP - 647

EP - 656

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 5

ER -