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Review
. 2015 May;20(5):647-656.
doi: 10.1038/mp.2014.107. Epub 2014 Oct 7.

Genome-wide Meta-Analysis Identifies Six Novel Loci Associated With Habitual Coffee Consumption

Coffee and Caffeine Genetics ConsortiumMarilyn C Cornelis  1   2 Enda M Byrne #  3 Tõnu Esko #  4   5   6   7 Michael A Nalls #  8 Andrea Ganna  9 Nina Paynter  10 Keri L Monda  11 Najaf Amin  12 Krista Fischer  4 Frida Renstrom  13 Julius S Ngwa  14 Ville Huikari  15 Alana Cavadino  16 Ilja M Nolte  17 Alexander Teumer  18 Kai Yu  19 Pedro Marques-Vidal  20 Rajesh Rawal  21 Ani Manichaikul  22 Mary K Wojczynski  23 Jacqueline M Vink  24 Jing Hua Zhao  25 George Burlutsky  26 Jari Lahti  27   28 Vera Mikkilä  29   30 Rozenn N Lemaitre  31 Joel Eriksson  32 Solomon K Musani  33 Toshiko Tanaka  34 Frank Geller  35 Jian'an Luan  25 Jennie Hui  36   37   38   39 Reedik Mägi  4 Maria Dimitriou  40 Melissa E Garcia  41 Weang-Kee Ho  42 Margaret J Wright  43 Lynda M Rose  10 Patrik Ke Magnusson  9 Nancy L Pedersen  9 David Couper  44 Ben A Oostra  45 Albert Hofman  12 Mohammad Arfan Ikram  12   46   47 Henning W Tiemeier  12   48 Andre G Uitterlinden  12   49 Frank Ja van Rooij  12 Inês Barroso  50   51 Ingegerd Johansson  52 Luting Xue  14 Marika Kaakinen  15   53   54 Lili Milani  4 Chris Power  16 Harold Snieder  17 Ronald P Stolk  17 Sebastian E Baumeister  55 Reiner Biffar  56 Fangyi Gu  19 François Bastardot  57 Zoltán Kutalik  58   59   60 David R Jacobs Jr  61 Nita G Forouhi  25 Evelin Mihailov  4 Lars Lind  62 Cecilia Lindgren  63 Karl Michaëlsson  64 Andrew Morris  63 Majken Jensen  2 Kay-Tee Khaw  42 Robert N Luben  42 Jie Jin Wang  26 Satu Männistö  65 Mia-Maria Perälä  65 Mika Kähönen  66 Terho Lehtimäki  67 Jorma Viikari  68 Dariush Mozaffarian  1   2   69 Kenneth Mukamal  70 Bruce M Psaty  31   71   72   73 Angela Döring  74 Andrew C Heath  75 Grant W Montgomery  43 Norbert Dahmen  76 Teresa Carithers  77 Katherine L Tucker  78 Luigi Ferrucci  34 Heather A Boyd  35 Mads Melbye  35 Jorien L Treur  24 Dan Mellström  32 Jouke Jan Hottenga  24 Inga Prokopenko  63   79 Anke Tönjes  80   81 Panos Deloukas  50   82   83 Stavroula Kanoni  82 Mattias Lorentzon  32 Denise K Houston  84 Yongmei Liu  84 John Danesh  42 Asif Rasheed  85 Marc A Mason  86 Alan B Zonderman  87 Lude Franke  88 Bruce S Kristal  89   90 International Parkinson’s Disease Genomics Consortium (IPDGC)North American Brain Expression Consortium (NABEC)UK Brain Expression Consortium (UKBEC)Juha Karjalainen  88 Danielle R Reed  91 Harm-Jan Westra  88 Michele K Evans  86 Danish Saleheen  42   85 Tamara B Harris  41 George Dedoussis  40 Gary Curhan  1 Michael Stumvoll  80   81 John Beilby  36   37   38 Louis R Pasquale  1   92 Bjarke Feenstra  35 Stefania Bandinelli  93 Jose M Ordovas  94 Andrew T Chan  1   95 Ulrike Peters  96 Claes Ohlsson  32 Christian Gieger  21 Nicholas G Martin  43 Melanie Waldenberger  97 David S Siscovick  31   71 Olli Raitakari  30   98 Johan G Eriksson  28   99   100 Paul Mitchell  26 David J Hunter  1   101 Peter Kraft  101 Eric B Rimm  1   2   69 Dorret I Boomsma  24 Ingrid B Borecki  23 Ruth Jf Loos  25   102   103 Nicholas J Wareham  25 Peter Vollenweider  57 Neil Caporaso  19 Hans Jörgen Grabe  104 Marian L Neuhouser  105 Bruce Hr Wolffenbuttel  106 Frank B Hu  1   2   69 Elina Hyppönen  16   107   108 Marjo-Riitta Järvelin  15   53   54   109   110 L Adrienne Cupples  14   111 Paul W Franks  2   13   112 Paul M Ridker  10 Cornelia M van Duijn  12   113 Gerardo Heiss  11 Andres Metspalu  4 Kari E North  11 Erik Ingelsson  62   63 Jennifer A Nettleton  114 Rob M van Dam  115 Daniel I Chasman  10
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Free PMC article
Review

Genome-wide Meta-Analysis Identifies Six Novel Loci Associated With Habitual Coffee Consumption

Coffee and Caffeine Genetics Consortium et al. Mol Psychiatry. .
Free PMC article

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<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.

Figures

Figure 1
Figure 1
Network describing direct interactions between candidate genes of confirmed loci. Relationships were retrieved from databases of transcription regulation and protein-protein interaction experiments (Supplementary Table S21). Genes are represented as nodes that are colored according to locus. Candidate genes for loci identified in the current study were supplemented with known candidate genes related to caffeine pharmacology (grey nodes). Edges indicate known interactions.

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