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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Caffeine; Protein; Variants; Receptor; Brain; Glucokinase; Involvement; Binding; Bdnf
Keywords plus
Sprache
Veröffentlichungsjahr
2015
Prepublished im Jahr
2014
HGF-Berichtsjahr
2014
ISSN (print) / ISBN
1359-4184
e-ISSN
1476-5578
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 20,
Heft: 5,
Seiten: 647-656
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Nature Publishing Group
Verlagsort
London
Tag d. mündl. Prüfung
0000-00-00
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Gutachter
Prüfer
Topic
Hochschule
Hochschulort
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Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504091-004
G-504091-001
G-500700-001
G-504000-002
Förderungen
Copyright
Erfassungsdatum
2014-10-09