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Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.
Wednesday,2015-03-04 14:16 America/Los_Angeles — zdrager
| Title | Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | 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, W-K, 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, K-T, Luben, RN, Wang, JJ, Männistö, S, Perälä, M-M, 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, H-J, Evans, MK, Saleheen, D, Harris, TB, Dedoussis, G, Curhan, G, Stumvoll, M, Beilby, J, Pasquale, LR, Feenstra, B, Bandinelli, S, Ordovás, 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, Järvelin, M-R, Cupples, LA, Franks, PW, Ridker, PM, van Duijn, CM, Heiss, G, Metspalu, A, North, KE, Ingelsson, E, Nettleton, JA, van Dam, RM, Chasman, DI |
| Corporate/Institutional Authors | Coffee and Caffeine Genetics Consortium, International Parkinson's Disease Genomics Consortium (IPDGC), North American Brain Expression Consortium (NABEC), UK Brain Expression Consortium (UKBEC) |
| Journal | Mol Psychiatry |
| Volume | 20 |
| Issue | 5 |
| Pagination | 647-56 |
| Date Published | 2015 May |
| ISSN | 1476-5578 |
| Keywords | Adaptor Proteins, Signal Transducing, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Brain-Derived Neurotrophic Factor, Coffea, Cytochrome P-450 CYP1A2, Food Habits, Genome-Wide Association Study, Humans, Phenotype, Polymorphism, Single Nucleotide |
| Abstract | <p>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.</p> |
| DOI | 10.1038/mp.2014.107 |
| Alternate Journal | Mol. Psychiatry |
| PubMed ID | 25288136 |
| PubMed Central ID | PMC4388784 |
| Grant List | 090532 / / Wellcome Trust / United Kingdom 14136 / / Cancer Research UK / United Kingdom G1000143 / / Medical Research Council / United Kingdom MC_U106179471 / / Medical Research Council / United Kingdom MC_UP_A100_1003 / / Medical Research Council / United Kingdom MC_UU_12015/1 / / Medical Research Council / United Kingdom MC_UU_12015/5 / / Medical Research Council / United Kingdom MR/L003120/1 / / Medical Research Council / United Kingdom P60 AA011998 / AA / NIAAA NIH HHS / United States R01 EY015473 / EY / NEI NIH HHS / United States R01 HL117078 / HL / NHLBI NIH HHS / United States R01 NS041509 / NS / NINDS NIH HHS / United States R01 NS075321 / NS / NINDS NIH HHS / United States RG/08/014/24067 / / British Heart Foundation / United Kingdom U01 HG004728 / HG / NHGRI NIH HHS / United States UM1 CA182913 / CA / NCI NIH HHS / United States |