A new, large-scale study has identified six new genetic variants associated with habitual coffee drinking. The genome-wide meta-analysis, led by Harvard School of Public Health and Brigham and Women's Hospital researchers, helps explain why a given amount of coffee or caffeine has different effects on different people and provides a genetic basis for future research exploring the links between coffee and health.
"Coffee and caffeine have been linked to beneficial and adverse health effects. Our findings may allow us to identify subgroups of people most likely to benefit from increasing or decreasing coffee consumption for optimal health," said Marilyn Cornelis, research associate in the Department of Nutrition at Harvard School of Public Health and lead author of the study.
The study appears online October 7, 2014 in Molecular Psychiatry.
Genetics have long been suspected of contributing to individual differences in response to coffee and caffeine. However, pinpointing the specific genetic variants has been challenging.
The researchers, part of the Coffee and Caffeine Genetics Consortium, conducted a genome-wide meta-analysis of more than 120,000 regular coffee drinkers of European and African American ancestry. They identified two variants that mapped to genes involved in caffeine metabolism, POR and ABCG2 (two others, AHR and CYP1A2 had been identified previously).
Two variants were identified near genes BDNF and SLC6A4 that potentially influence the rewarding effects of caffeine. Two others—near GCKR and MLXIPL, genes involved in glucose and lipid metabolism—had not previously been linked to the metabolism or neurological effects of coffee.
The findings suggest that people naturally modulate their coffee intake to experience the optimal effects exerted by caffeine and that the strongest genetic factors linked to increased coffee intake likely work by directly increasing caffeine metabolism.
"The new candidate genes are not the ones we have focused on in the past, so this is an important step forward in coffee research," said Cornelis.
"Like previous genetic analyses of smoking and alcohol consumption, this research serves as an example of how genetics can influence some types of habitual behavior," said Daniel Chasman, associate professor at Brigham and Women's Hospital and the study's senior author.
"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, Mohammad Arfan Ikram, Henning W Tiemeier, Andre G Uitterlinden, Frank JA van Rooij, Inês Barroso, Ingegerd Johansson, Luting Xue, Marika Kaakinen, Lili Milani, Christine Power, Harold Snieder, Ronald P Stolk, Sebastian E Baumeister, Reiner Biffar, Fangyi Gu, François Bastardot, Zoltán Kutalik, David R Jacobs Jr , Nita G Forouhi, Evelin Mihailov, Lars Lind, Cecilia Lindgren, Karl Michaëlsson, Andrew Morris, Majken Jensen, Kay-Tee Khaw, Robert N Luben, Jie Jin Wang, Satu Männistö, Mia-Maria Perälä, Mika Kähönen, 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, International Parkinson's Disease Genomics Consortium (IPDGC), North American Brain Expression Consortium (NABEC), UK Brain Expression Consortium (UKBEC), 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 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 M van Duijn, Gerardo Heiss, Andres Metspalu, Kari E North, Erik Ingelsson, Jennifer A Nettleton, Rob M van Dam, and Daniel I Chasman, Molecular Psychiatry, online October 7, 2014, doi: 10.1038/mp.2014.107
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