“Genome-Wide Meta-Analysis Identifies Six Novel Loci Associated With Habitual Coffee Consumption”, Marilyn C. Cornelis, Enda M. Byrne, Tõnu Esko, Michael A. Nalls, Andrea Ganna, Nina Paynter, Keri L. Monda, Najaf Amin, Krista Fischer, Frida Renstrom, Julius S. Ngwa, Ville Huikari, Alana Cavadino, Ilja M. Nolte, Alexander Teumer, Kai Yu, Pedro Marques-Vidal, Rajesh Rawal, Ani Manichaikul, Mary K. Wojczynski, Jacqueline M. Vink, Jing Hua Zhao, George Burlutsky, Jari Lahti, Vera Mikkilä, Rozenn N. Lemaitre, Joel Eriksson, Solomon K. Musani, Toshiko Tanaka, Frank Geller, Jian’an Luan, Jennie Hui, Reedik Mägi, Maria Dimitriou, Melissa E. Garcia, Weang-Kee Ho, Margaret J. Wright, Lynda M. Rose, Patrik Ke Magnusson, Nancy L. Pedersen, David Couper, Ben A. Oostra, Albert Hofman, M. Arfan Ikram, Henning W. Tiemeier, André G. Uitterlinden, Frank Ja van Rooij, Inês Barroso, Ingegerd Johansson, Luting Xue, Marika Kaakinen, Lili Milani, Chris Power, Harold Snieder, Ronald P. Stolk, Sebastian E. Baumeister, Reiner Biffar, Fangyi Gu, François Bastardot, Zoltán Kutalik, David R. Jacobs, Nita G. Forouhi, Evelin Mihailov, Lars L. Lind, Cecilia M. Lindgren, Karl Michaëlsson, Andrew P. Morris, Majken Jensen, Kay-Tee Khaw, Robert N. Luben, Jie Jin Wang, Satu Männistö, Mia-Maria Perälä, Kähönen Mika, Terho Lehtimäki, Jorma Viikari, Dariush Mozaffarian, Kenneth Mukamal, Bruce M. Psaty, Angela Döring, Andrew C. Heath, Grant W. Montgomery, Norbert Dahmen, Teresa Carithers, Katherine L. Tucker, Luigi Ferrucci, Heather A. Boyd, Mads Melbye, Jorien L. Treur, Dan Mellström, Jouke Jan Hottenga, Inga Prokopenko, Anke Tönjes, Panos Deloukas, Stavroula Kanoni, Mattias Lorentzon, Denise K. Houston, Yongmei Liu, John Danesh, Asif Rasheed, Marc A. Mason, Alan B. Zonderman, Lude Franke, Bruce S. Kristal, Juha Karjalainen, Danielle R. Reed, Harm-Jan Westra, Michele K. Evans, Danish Saleheen, Tamara B. Harris, George Dedoussis, Gary Curhan, Michael Stumvoll, John Beilby, Louis R. Pasquale, Bjarke Feenstra, Stefania Bandinelli, Jose M. Ordovas, Andrew T. Chan, Ulrike Peters, Claes Ohlsson, Christian Gieger, Nicholas G. Martin, Melanie Waldenberger, David S. Siscovick, Olli T. Raitakari, Johan G. Eriksson, Paul Mitchell, David J. Hunter, Peter Kraft, Eric B. Rimm, Dorret I. Boomsma, Ingrid B. Borecki, Ruth Jf Loos, Nicholas J. Wareham, Peter Vollenweider, Neil Caporaso, Hans Jörgen Grabe, Marian L. Neuhouser, Bruce Hr Wolffenbuttel, Frank B. Hu, Elina Hyppönen, Marjo-Riitta Järvelin, L. Adrienne Cupples, Paul W. Franks, Paul M. Ridker, Cornelia van Duijn, Gerardo Heiss, Andres Metspalu, Kari E. North, Erik Ingelsson, Jennifer A. Nettleton, Rob M. van Dam, Daniel I. Chasman2015 (heritability, caffeine, tea; backlinks; similar):
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 6 novel loci, met genome-wide statistical-significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03–0.14 cups per day. 6 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.