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Coffee and Caffeine Genetics Consortium ; Cornelis, M.C.* ; Byrne, E.M.* ; Esko, T.* ; Nalls, M.A.* ; Ganna, A.* ; Paynter, N.* ; Monda, K.L.* ; Amin, N.* ; Fischer, K.* ; Renström, 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.* ; Pedersen, N.L.* ; Couper, D.* ; Oostra, B.A.* ; Hofman, A.* ; Ikram, M.A.* ; Tiemeier, H.W.* ; Uitterlinden, A.G.* ; van Rooij, F.J.* ; 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.* ; Michaelsson, 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.J.* ; 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.* ; International Parkinson's Disease Genomics Consortium (IPDGC) (Illig, T. ; Lichtner, P.) ; North American Brain Expression Consortium (*) ; UK Brain Expression Consortium (*) ; 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.* ; Wareham, N.J.* ; Vollenweider, P.* ; Caporaso, N.* ; Grabe, H.J.* ; Neuhouser, M.L.* ; Wolffenbuttel, B.H.* ; Hu, F.B.* ; Hyppönen, E.* ; Jarvelin, 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.* ; Chasman, D.I.*

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

Mol. Psychiatry 20, 647-656 (2015)
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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 (log10Bayes 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Caffeine; Protein; Variants; Receptor; Brain; Glucokinase; Involvement; Binding; Bdnf
Language
Publication Year 2015
Prepublished in Year 2014
HGF-reported in Year 2014
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Journal Molecular Psychiatry
Quellenangaben Volume: 20, Issue: 5, Pages: 647-656 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
POF-Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504091-004
G-504091-001
G-500700-001
G-504000-002
DOI 10.1038/mp.2014.107
WOS ID WOS:000353706400016
Scopus ID 84929128366
PubMed ID 25288136
Erfassungsdatum 2014-10-09
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