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 (US) |
|---|---|
| Pages (from-to) | 647-656 |
| Number of pages | 10 |
| Journal | Molecular psychiatry |
| Volume | 20 |
| Issue number | 5 |
| DOIs |
|
| State | Published - May 30 2015 |
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Molecular Biology
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In: Molecular psychiatry, Vol. 20, No. 5, 30.05.2015, p. 647-656.
Research output: Contribution to journal › Comment/debate › peer-review
}
TY - JOUR
T1 - Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption
AU - Cornelis, M. C.
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AU - Wolffenbuttel, B. H.R.
AU - Hu, F. B.
AU - Hyppönen, E.
AU - Järvelin, M. R.
AU - Cupples, L. A.
AU - Franks, P. W.
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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 - Gibbs, J. Raphael
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
N1 - Publisher Copyright: © 2015 Macmillan Publishers Limited.
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 - http://www.scopus.com/inward/record.url?scp=84929128366&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929128366&partnerID=8YFLogxK
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 -