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; Chris 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; North American Brain Expression Consortium (NABEC)

doi:10.1038/mp.2014.107

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Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

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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, …

Molecular psychiatry, Vol.20(5), pp.647-656

01/05/2015

DOI: https://doi.org/10.1038/mp.2014.107

PMID: 25288136

Abstract

Adaptor Proteins, Signal Transducing - genetics

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics

Brain-Derived Neurotrophic Factor - genetics

Coffea - metabolism

Cytochrome P-450 CYP1A2 - genetics

Feeding Behavior

Genome-Wide Association Study

Humans

Phenotype

Polymorphism, Single Nucleotide - genetics

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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Title: Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption
Creators: Marilyn C Cornelis - Harvard University
Enda M Byrne - University of Queensland
Tõnu Esko - University of Tartu
Michael A Nalls - National Institute on Aging
Andrea Ganna - Karolinska Institutet
Nina Paynter - Brigham and Women's Hospital
Keri L Monda - University of North Carolina at Chapel Hill
Najaf Amin - Erasmus MC
Krista Fischer - University of Tartu
Frida Renstrom - Lund University
Julius S Ngwa - Boston University
Ville Huikari - University of Oulu
Alana Cavadino - University College London
Ilja M Nolte - University Medical Center Groningen
Alexander Teumer - Universitätsmedizin Greifswald
Kai Yu - National Cancer Institute
Pedro Marques-Vidal - University Hospital of Lausanne
Rajesh Rawal - Helmholtz Zentrum München
Ani Manichaikul - University of Virginia
Mary K Wojczynski - Washington University in St. Louis
Jacqueline M Vink - University of Amsterdam
Jing Hua Zhao - MRC Epidemiology Unit
George Burlutsky - Westmead Institute
Jari Lahti - University of Helsinki
Vera Mikkilä - University of Helsinki
Rozenn N Lemaitre - University of Washington
Joel Eriksson - University of Gothenburg
Solomon K Musani - University of Mississippi Medical Center
Toshiko Tanaka - National Institute on Aging
Frank Geller - Statens Serum Institut
Jian'an Luan - University of Cambridge
Jennie Hui - School of Population Health, The University of Western Australia, Nedlands, Western Australia
Reedik Mägi - University of Tartu
Maria Dimitriou - Harokopio University of Athens
Melissa E Garcia - National Institute on Aging
Weang-Kee Ho - University of Cambridge
Margaret J Wright - QIMR Berghofer Medical Research Institute
Lynda M Rose - Brigham and Women's Hospital
Patrik Ke Magnusson - Karolinska Institutet
Nancy L Pedersen - Karolinska Institutet
David Couper - University of North Carolina at Chapel Hill
Ben A Oostra - Erasmus MC
Albert Hofman - Erasmus MC
Mohammad Arfan Ikram - Erasmus MC
Henning W Tiemeier - Erasmus MC
Andre G Uitterlinden - Erasmus MC
Frank Ja van Rooij - Erasmus MC
Inês Barroso - Wellcome Sanger Institute
Ingegerd Johansson - Umeå University
Luting Xue - Boston University
Marika Kaakinen - University of Oulu
Lili Milani - University of Tartu
Chris Power - University College London
Harold Snieder - University Medical Center Groningen
Ronald P Stolk - University Medical Center Groningen
Sebastian E Baumeister - Universitätsmedizin Greifswald
Reiner Biffar - Universitätsmedizin Greifswald
Fangyi Gu - National Cancer Institute
François Bastardot - University Hospital of Lausanne
Zoltán Kutalik - University of Lausanne
David R Jacobs, Jr - University of Minnesota
Nita G Forouhi - MRC Epidemiology Unit
Evelin Mihailov - University of Tartu
Lars Lind - Erasmus MC
Cecilia Lindgren - University of Oxford
Karl Michaëlsson - Uppsala University
Andrew Morris - University of Oxford
Majken Jensen - Harvard University
Kay-Tee Khaw - University of Cambridge
Robert N Luben - University of Cambridge
Jie Jin Wang - Westmead Institute
Satu Männistö - Finnish Institute for Health and Welfare
Mia-Maria Perälä - Finnish Institute for Health and Welfare
Mika Kähönen - Tampere University
Terho Lehtimäki - Fimlab
Jorma Viikari - Turku University Hospital
Dariush Mozaffarian - Harvard University
Kenneth Mukamal - Beth Israel Deaconess Medical Center
Bruce M Psaty - University of Washington
Angela Döring - Helmholtz Zentrum München
Andrew C Heath - Washington University in St. Louis
Grant W Montgomery - QIMR Berghofer Medical Research Institute
Norbert Dahmen - Johannes Gutenberg University Mainz
Teresa Carithers - University of Mississippi
Katherine L Tucker - University of Massachusetts Lowell
Luigi Ferrucci - National Institute on Aging
Heather A Boyd - Statens Serum Institut
Mads Melbye - Statens Serum Institut
Jorien L Treur - University of Amsterdam
Dan Mellström - University of Gothenburg
Jouke Jan Hottenga - University of Amsterdam
Inga Prokopenko - Wellcome Centre for Human Genetics
Anke Tönjes - Leipzig University
Panos Deloukas - Wellcome Sanger Institute
Stavroula Kanoni - Queen Mary University of London
Mattias Lorentzon - University of Gothenburg
Denise K Houston - Wake Forest University
Yongmei Liu - Wake Forest University
John Danesh - University of Cambridge
Asif Rasheed - Center for Non-Communicable Diseases
North American Brain Expression Consortium (NABEC)
Publication Details: Molecular psychiatry, Vol.20(5), pp.647-656
Date published: 01/05/2015
Grant note: G0401527 / Medical Research Council R01 HL120393 / NHLBI NIH HHS MC_UU_12015/1 / Medical Research Council MC_UU_12015/5 / Medical Research Council RG/13/13/30194 / British Heart Foundation U01 HG004728 / NHGRI NIH HHS MR/L003120/1 / Medical Research Council MC_UP_A100_1003 / Medical Research Council R01 HL105756 / NHLBI NIH HHS P60 AA011998 / NIAAA NIH HHS
Identifiers: 99928955402346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

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