Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption
Journal article
Cornelis, Marilyn C., Byrne, Enda M., Esko, Tonu, Nalls, Michael A., Ganna, Andrea, Paynter, Nina, Monda, Keri L., Amin, Najaf, Fischer, Krista, Renstrom, Frida, Ngwa, Julius S., Huikari, Ville, Cavadino, Alana, Nolte, Ilja M., Teumer, Alexander, Yu, Kai, Marques-Vidal, Pedro Manuel, Rawal, Rajesh, Manichaikul, Ani, ... UK Brain Expression Consortium (UKBEC). (2015). Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Molecular Psychiatry. 20(5), pp. 647-656. https://doi.org/10.1038/mp.2014.107
Authors | Cornelis, Marilyn C., Byrne, Enda M., Esko, Tonu, Nalls, Michael A., Ganna, Andrea, Paynter, Nina, Monda, Keri L., Amin, Najaf, Fischer, Krista, Renstrom, Frida, Ngwa, Julius S., Huikari, Ville, Cavadino, Alana, Nolte, Ilja M., Teumer, Alexander, Yu, Kai, Marques-Vidal, Pedro Manuel, Rawal, Rajesh, Manichaikul, Ani, Wojczynski, Mary K., Vink, Jacqueline M., Zhao, Jing, Burlutsky, George, Lahti, Jari, Mikkilä, Vera, Lemaitre, Rozenn N., Eriksson, Joel, Musani, Solomon K., Tanaka, Toshiko, 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. E., Pedersen, N. L., Couper, D., Oostra, B. A., Hofman, A., Ikram, M. A., Tiemeier, H. W., Uitterlinden, A. G., van Rooij, F. J. A., 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., Michaëlsson, 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., 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),, North American Brain Expression Consortium (NABEC),, UK Brain Expression Consortium (UKBEC),, 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. F., Wareham, N. J., Vollenweider, P., Caporaso, N., Grabe, H. J., Neuhouser, M. L., Wolffenbuttel, B. H. R., Hu, F. B., Hyppönen, E., Järvelin, 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., International Parkinson's Disease Genomics Consortium (IPDGC), North American Brain Expression Consortium (NABEC) and UK Brain Expression Consortium (UKBEC) |
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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 ~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× 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. |
Year | 2015 |
Journal | Molecular Psychiatry |
Journal citation | 20 (5), pp. 647-656 |
Publisher | Nature Publishing Group |
ISSN | 1359-4184 |
Digital Object Identifier (DOI) | https://doi.org/10.1038/mp.2014.107 |
Scopus EID | 2-s2.0-84929128366 |
Open access | Published as green open access |
Page range | 647-656 |
Research Group | Mary MacKillop Institute for Health Research |
Author's accepted manuscript | License All rights reserved File Access Level Open |
Publisher's version | License All rights reserved File Access Level Controlled |
Output status | Published |
Publication dates | |
Online | 07 Oct 2014 |
Publication process dates | |
Accepted | 22 Jul 2014 |
Additional information | Study-specific funding and acknowledgments are provided in the Supplementary Information (https://www.nature.com/articles/mp2014107#MOESM349). We collectively thank everyone who has contributed to the collection, genotyping and analysis of the individual cohorts, as well as all the study participants. |
https://acuresearchbank.acu.edu.au/item/874v6/genome-wide-meta-analysis-identifies-six-novel-loci-associated-with-habitual-coffee-consumption
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