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

MC Cornelis; EM Byrne; T Esko; MA Nalls; A Ganna; N Paynter; KL Monda; Najaf Amin; K (Kirsten) Fischer; F Renstrom; JS Ngwa; V Huikari; A Cavadino; IM (Ilja) Nolte; A Teumer; Carol Yu; P Marques-Vidal; R Rawal; A Manichaikul; MK Wojczynski; JM Vink; JH Zhao; G Burlutsky; J Lahti; V Mikkila; RN Lemaitre; J Eriksson; SK Musani; T Tanaka; F Geller; J Luan; J Hui; R Magi; M Dimitriou; ME Garcia; WK Ho; MJ Wright; LM Rose; PKE Magnusson; NL Pedersen; D Couper; Ben Oostra; Bert Hofman; Arfan Ikram; Henning Tiemeier; André Uitterlinden; FJA van Rooij; I Barroso; I Johansson; L Xue; M Kaakinen; L Milani; C Power; H Snieder; RP (Ronald) Stolk; SE Baumeister; R Biffar; F Gu; F Bastardot; Z Kutalik; DR Jacobs; NG Forouhi; E Mihailov; L Lind; C Lindgren; K Michaelsson; A Morris; M Jensen; KT Khaw; RN Luben; JJ Wang; S Mannisto; MM Perala; M Kahonen; T Lehtimaki; J Viikari; D Mozaffarian; K Mukamal; BM Psaty; A Doring; AC Heath; GW Montgomery; N Dahmen; T Carithers; KL Tucker; L Ferrucci; HA Boyd; M Melbye; JL Treur; D Mellstrom; JJ (Jouke Jan) Hottenga; I Prokopenko; A Tonjes; P Deloukas; S Kanoni; M Lorentzon; DK Houston; Y Liu; J Danesh; A Rasheed; MA Mason; AB Zonderman; L Franke; BS Kristal; J Karjalainen; DR Reed; HJ Westra; MK Evans; D Saleheen; TB Harris; G Dedoussis; G Curhan; M Stumvoll; J Beilby; LR Pasquale; B Feenstra; S Bandinelli; JM Ordovas; AT Chan; U Peters; C Ohlsson; C Gieger; NG Martin; M Waldenberger; DS Siscovick; O Raitakari; JG Eriksson; P Mitchell; DJ Hunter; P Kraft; EB Rimm; DI Boomsma; IB Borecki; RJF Loos; NJ Wareham; P Vollenweider; N Caporaso; HJ Grabe; ML Neuhouser; BHR Wolffenbuttel; FB Hu; E Hypponen; MR Jarvelin; LA Cupples; PW Franks; PM Ridker; Cornelia Duijn; G Heiss; A Metspalu; KE North; E Ingelsson; JA Nettleton; RM van Dam; DI Chasman

doi:10.1038/mp.2014.107

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

MC Cornelis, EM Byrne, T Esko, MA Nalls, A Ganna, N Paynter, KL Monda, Najaf Amin, K (Kirsten) Fischer, F Renstrom, JS Ngwa, V Huikari, A Cavadino, IM (Ilja) Nolte, A Teumer, Carol Yu, P Marques-Vidal, R Rawal, A Manichaikul, MK WojczynskiJM Vink, JH Zhao, G Burlutsky, J Lahti, V Mikkila, RN Lemaitre, J Eriksson, SK Musani, T Tanaka, F Geller, J Luan, J Hui, R Magi, M Dimitriou, ME Garcia, WK Ho, MJ Wright, LM Rose, PKE Magnusson, NL Pedersen, D Couper, Ben Oostra, Bert Hofman, Arfan Ikram, Henning Tiemeier, André Uitterlinden, FJA van Rooij, I Barroso, I Johansson, L Xue, M Kaakinen, L Milani, C Power, H Snieder, RP (Ronald) Stolk, SE Baumeister, R Biffar, F Gu, F Bastardot, Z Kutalik, DR Jacobs, NG Forouhi, E Mihailov, L Lind, C Lindgren, K Michaelsson, A Morris, M Jensen, KT Khaw, RN Luben, JJ Wang, S Mannisto, MM Perala, M Kahonen, T Lehtimaki, J Viikari, D Mozaffarian, K Mukamal, BM Psaty, A Doring, AC Heath, GW Montgomery, N Dahmen, T Carithers, KL Tucker, L Ferrucci, HA Boyd, M Melbye, JL Treur, D Mellstrom, JJ (Jouke Jan) Hottenga, I Prokopenko, A Tonjes, P Deloukas, S Kanoni, M Lorentzon, DK Houston, Y Liu, J Danesh, A Rasheed, MA Mason, AB Zonderman, L Franke, BS Kristal, J Karjalainen, DR Reed, HJ Westra, MK Evans, D Saleheen, TB Harris, G Dedoussis, G Curhan, M Stumvoll, J Beilby, LR Pasquale, B Feenstra, S Bandinelli, JM Ordovas, AT Chan, U Peters, C Ohlsson, C Gieger, NG Martin, M Waldenberger, DS Siscovick, O Raitakari, JG Eriksson, P Mitchell, DJ Hunter, P Kraft, EB Rimm, DI Boomsma, IB Borecki, RJF Loos, NJ Wareham, P Vollenweider, N Caporaso, HJ Grabe, ML Neuhouser, BHR Wolffenbuttel, FB Hu, E Hypponen, MR Jarvelin, LA Cupples, PW Franks, PM Ridker, Cornelia Duijn, G Heiss, A Metspalu, KE North, E Ingelsson, JA Nettleton, RM van Dam, DI Chasman

Research output: Contribution to journal › Article › Academic › peer-review

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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 similar to 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 < 5x10(-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	Undefined/Unknown
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 - 2015

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10.1038/mp.2014.107

http://hdl.handle.net/1765/85083

Cite this

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, C., Marques-Vidal, P., Rawal, R., Manichaikul, A., ... Chasman, DI. (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{773753cddf9049659dc475a1a98b5bad,

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 similar to 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 < 5x10(-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 = "MC Cornelis and EM Byrne and T Esko and MA Nalls and A Ganna and N Paynter and KL Monda and Najaf Amin and Fischer, {K (Kirsten)} and F Renstrom and JS Ngwa and V Huikari and A Cavadino and Nolte, {IM (Ilja)} and A Teumer and Carol Yu and P Marques-Vidal and R Rawal and A Manichaikul and MK Wojczynski and JM Vink and JH Zhao and G Burlutsky and J Lahti and V Mikkila and RN Lemaitre and J Eriksson and SK Musani and T Tanaka and F Geller and J Luan and J Hui and R Magi and M Dimitriou and ME Garcia and WK Ho and MJ Wright and LM Rose and PKE Magnusson and NL Pedersen and D Couper and Ben Oostra and Bert Hofman and Arfan Ikram and Henning Tiemeier and Andr{\'e} Uitterlinden and {van Rooij}, FJA and I Barroso and I Johansson and L Xue and M Kaakinen and L Milani and C Power and H Snieder and Stolk, {RP (Ronald)} and SE Baumeister and R Biffar and F Gu and F Bastardot and Z Kutalik and DR Jacobs and NG Forouhi and E Mihailov and L Lind and C Lindgren and K Michaelsson and A Morris and M Jensen and KT Khaw and RN Luben and JJ Wang and S Mannisto and MM Perala and M Kahonen and T Lehtimaki and J Viikari and D Mozaffarian and K Mukamal and BM Psaty and A Doring and AC Heath and GW Montgomery and N Dahmen and T Carithers and KL Tucker and L Ferrucci and HA Boyd and M Melbye and JL Treur and D Mellstrom and Hottenga, {JJ (Jouke Jan)} and I Prokopenko and A Tonjes and P Deloukas and S Kanoni and M Lorentzon and DK Houston and Y Liu and J Danesh and A Rasheed and MA Mason and AB Zonderman and L Franke and BS Kristal and J Karjalainen and DR Reed and HJ Westra and MK Evans and D Saleheen and TB Harris and G Dedoussis and G Curhan and M Stumvoll and J Beilby and LR Pasquale and B Feenstra and S Bandinelli and JM Ordovas and AT Chan and U Peters and C Ohlsson and C Gieger and NG Martin and M Waldenberger and DS Siscovick and O Raitakari and JG Eriksson and P Mitchell and DJ Hunter and P Kraft and EB Rimm and DI Boomsma and IB Borecki and RJF Loos and NJ Wareham and P Vollenweider and N Caporaso and HJ Grabe and ML Neuhouser and BHR Wolffenbuttel and FB Hu and E Hypponen and MR Jarvelin and LA Cupples and PW Franks and PM Ridker and Cornelia Duijn and G Heiss and A Metspalu and KE North and E Ingelsson and JA Nettleton and {van Dam}, RM and DI Chasman",

year = "2015",

doi = "10.1038/mp.2014.107",

language = "Undefined/Unknown",

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, C, Marques-Vidal, P, Rawal, R, Manichaikul, A, Wojczynski, MK, Vink, JM, Zhao, JH, Burlutsky, G, Lahti, J, Mikkila, V, Lemaitre, RN, Eriksson, J, Musani, SK, Tanaka, T, Geller, F, Luan, J, Hui, J, Magi, R, Dimitriou, M, Garcia, ME, Ho, WK, Wright, MJ, Rose, LM, Magnusson, PKE, Pedersen, NL, Couper, D, Oostra, B, Hofman, B , Ikram, A , Tiemeier, H , Uitterlinden, A , 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, Michaelsson, K, Morris, A, Jensen, M, Khaw, KT, Luben, RN, Wang, JJ, Mannisto, S, Perala, MM, Kahonen, M, Lehtimaki, T, Viikari, J, Mozaffarian, D, Mukamal, K, Psaty, BM, Doring, A, Heath, AC, Montgomery, GW, Dahmen, N, Carithers, T, Tucker, KL, Ferrucci, L, Boyd, HA, Melbye, M, Treur, JL, Mellstrom, D, Hottenga, JJ, Prokopenko, I, Tonjes, 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, Hypponen, E, Jarvelin, MR, Cupples, LA, Franks, PW, Ridker, PM, Duijn, C, Heiss, G, Metspalu, A, North, KE, Ingelsson, E, Nettleton, JA, van Dam, RM & Chasman, DI 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, MC

AU - Byrne, EM

AU - Esko, T

AU - Nalls, MA

AU - Ganna, A

AU - Paynter, N

AU - Monda, KL

AU - Amin, Najaf

AU - Fischer, K (Kirsten)

AU - Renstrom, F

AU - Ngwa, JS

AU - Huikari, V

AU - Cavadino, A

AU - Nolte, IM (Ilja)

AU - Teumer, A

AU - Yu, Carol

AU - Marques-Vidal, P

AU - Rawal, R

AU - Manichaikul, A

AU - Wojczynski, MK

AU - Vink, JM

AU - Zhao, JH

AU - Burlutsky, G

AU - Lahti, J

AU - Mikkila, V

AU - Lemaitre, RN

AU - Eriksson, J

AU - Musani, SK

AU - Tanaka, T

AU - Geller, F

AU - Luan, J

AU - Hui, J

AU - Magi, R

AU - Dimitriou, M

AU - Garcia, ME

AU - Ho, WK

AU - Wright, MJ

AU - Rose, LM

AU - Magnusson, PKE

AU - Pedersen, NL

AU - Couper, D

AU - Oostra, Ben

AU - Hofman, Bert

AU - Ikram, Arfan

AU - Tiemeier, Henning

AU - Uitterlinden, André

AU - van Rooij, FJA

AU - Barroso, I

AU - Johansson, I

AU - Xue, L

AU - Kaakinen, M

AU - Milani, L

AU - Power, C

AU - Snieder, H

AU - Stolk, RP (Ronald)

AU - Baumeister, SE

AU - Biffar, R

AU - Gu, F

AU - Bastardot, F

AU - Kutalik, Z

AU - Jacobs, DR

AU - Forouhi, NG

AU - Mihailov, E

AU - Lind, L

AU - Lindgren, C

AU - Michaelsson, K

AU - Morris, A

AU - Jensen, M

AU - Khaw, KT

AU - Luben, RN

AU - Wang, JJ

AU - Mannisto, S

AU - Perala, MM

AU - Kahonen, M

AU - Lehtimaki, T

AU - Viikari, J

AU - Mozaffarian, D

AU - Mukamal, K

AU - Psaty, BM

AU - Doring, A

AU - Heath, AC

AU - Montgomery, GW

AU - Dahmen, N

AU - Carithers, T

AU - Tucker, KL

AU - Ferrucci, L

AU - Boyd, HA

AU - Melbye, M

AU - Treur, JL

AU - Mellstrom, D

AU - Hottenga, JJ (Jouke Jan)

AU - Prokopenko, I

AU - Tonjes, A

AU - Deloukas, P

AU - Kanoni, S

AU - Lorentzon, M

AU - Houston, DK

AU - Liu, Y

AU - Danesh, J

AU - Rasheed, A

AU - Mason, MA

AU - Zonderman, AB

AU - Franke, L

AU - Kristal, BS

AU - Karjalainen, J

AU - Reed, DR

AU - Westra, HJ

AU - Evans, MK

AU - Saleheen, D

AU - Harris, TB

AU - Dedoussis, G

AU - Curhan, G

AU - Stumvoll, M

AU - Beilby, J

AU - Pasquale, LR

AU - Feenstra, B

AU - Bandinelli, S

AU - Ordovas, JM

AU - Chan, AT

AU - Peters, U

AU - Ohlsson, C

AU - Gieger, C

AU - Martin, NG

AU - Waldenberger, M

AU - Siscovick, DS

AU - Raitakari, O

AU - Eriksson, JG

AU - Mitchell, P

AU - Hunter, DJ

AU - Kraft, P

AU - Rimm, EB

AU - Boomsma, DI

AU - Borecki, IB

AU - Loos, RJF

AU - Wareham, NJ

AU - Vollenweider, P

AU - Caporaso, N

AU - Grabe, HJ

AU - Neuhouser, ML

AU - Wolffenbuttel, BHR

AU - Hu, FB

AU - Hypponen, E

AU - Jarvelin, MR

AU - Cupples, LA

AU - Franks, PW

AU - Ridker, PM

AU - Duijn, Cornelia

AU - Heiss, G

AU - Metspalu, A

AU - North, KE

AU - Ingelsson, E

AU - Nettleton, JA

AU - van Dam, RM

AU - Chasman, DI

PY - 2015

Y1 - 2015

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 similar to 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 < 5x10(-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 similar to 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 < 5x10(-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.

U2 - 10.1038/mp.2014.107

DO - 10.1038/mp.2014.107

M3 - Article

C2 - 25288136

SN - 1359-4184

VL - 20

SP - 647

EP - 656

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 5

ER -