6533b861fe1ef96bd12c4f52
RESEARCH PRODUCT
Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption
Coffee And Caffeine Genetics ConsortiumMarilyn C CornelisFrida RenstromAsif RasheedMarc A MasonAlan B ZondermanLude FrankeBruce S KristalInternational Parkinson’s Disease Genomics ConsortiumNorth American Brain Expression ConsortiumUk Brain Expression ConsortiumJuha KarjalainenDanielle R ReedJulius S NgwaHarm-jan WestraMichele K EvansDanish SaleheenTamara B HarrisGeorge DedoussisGary CurhanMichael StumvollJohn BeilbyLouis R PasqualeBjarke FeenstraVille HuikariStefania BandinelliJose M OrdovasAndrew T ChanUlrike PetersClaes OhlssonChristian GiegerNicholas G MartinMelanie WaldenbergerDavid S SiscovickOlli RaitakariAlana CavadinoJohan G ErikssonPaul MitchellDavid J HunterPeter KraftEric B RimmDorret I BoomsmaIngrid B BoreckiRuth Jf LoosNicholas J WarehamPeter VollenweiderIlja M NolteNeil CaporasoHans Jörgen GrabeMarian L NeuhouserBruce Hr WolffenbuttelFrank B HuElina HyppönenMarjo-riitta JärvelinL Adrienne CupplesPaul W FranksPaul M RidkerAlexander TeumerCornelia M Van DuijnGerardo HeissAndres MetspaluKari E NorthErik IngelssonJennifer A NettletonRob M Van DamDaniel I ChasmanMichael A NallsVincent PlagnolKai YuDena G HernandezManu SharmaUna-marie SheerinMohamad SaadJavier Simón-sánchezClaudia SchulteSuzanne LesageSigurlaug SveinbjörnsdóttirSampath ArepalliRoger BarkerPedro Marques-vidalYoav Ben-shlomoHenk W BerendseDaniela BergKailash BhatiaRob M A De BieAlessandro BiffiBas BloemZoltan BochdanovitsMichael BoninM. BrasRajesh RawalKathrin BrockmannJanet BrooksDavid J BurnGavin CharlesworthHonglei ChenPatrick F ChinnerySean ChongCarl E ClarkeMark R CooksonJ Mark CooperAni ManichaikulJean Christophe CorvolCarl CounsellPhilippe DamierJean-françois DartiguesPanos DeloukasGünther DeuschlDavid T DexterKarin D Van DijkAllissa DillmanFrank DurifEnda M ByrneMary K WojczynskiAlexandra DürrSarah EdkinsJonathan R EvansThomas FoltynieJing DongMichelle GardnerJ Raphael GibbsAlison GoateEmma GrayRita GuerreiroJacqueline M VinkClare HarrisJacobus J Van HiltenAlbert HofmanAlbert HollenbeckJanice HoltonMichele HuXuemei HuangMilton S HersheyIsabel WursterWalter MätzlerJing Hua ZhaoGavin HudsonSarah E HuntJohanna HuttenlocherThomas IlligHelmholtz Zentrum MünchenPálmi V JónssonJean-charles LambertCordelia LangfordAndrew LeesPeter LichtnerGeorge BurlutskyHelmholtz Zentrum MünchenPatricia LimousinGrisel LopezDelia LorenzAlisdair McneillCatriona MoorbyMatthew MooreHuw R MorrisKaren E MorrisonSean S O' SullivanJari LahtiJustin PearsonJoel S PerlmutterHjörvar PéturssonPierre PollakSimon PotterBernard RavinaTamas ReveszOlaf RiessFernando RivadeneiraPatrizia RizzuVera MikkiläMina RytenStephen SawcerAnthony SchapiraHans SchefferKaren ShawEllen SidranskyColin SmithChris C A SpencerHreinn StefánssonFrancesco BettellaRozenn N LemaitreJoanna D StocktonAmy StrangeKevin TalbotM. TannerAvazeh Tashakkori-ghanbariaFrançois TisonDaniah TrabzuniBryan J TraynorAndré G UitterlindenDaan VelseboerJoel ErikssonMarie VidailhetRobert WalkerBart Van De WarrenburgMirdhu WickremaratchiNigel WilliamsCaroline H Williams-graySophie Winder-rhodesKári StefánssonMaria MartinezPaul SabatierSolomon K MusaniNicholas W WoodJohn HardyPeter HeutinkAlexis BriceThomas GasserAndrew B SingletonAndrew SingletonMark CooksonJ Raphael GibbsDena HernandezToshiko TanakaAllissa DillmanMichael NallsAlan ZondermanSampath ArepalliLuigi FerrucciRobert JohnsonDan LongoRichard O'brienBryan TraynorJuan TroncosoTõnu EskoFrank GellerMarcel Van Der BrugRonald ZielkeJohn HardyMichael WealeMina RytenAdaikalavan RamasamyDaniah TrabzuniP. O. BoxColin SmithRobert WalkerJian'an LuanJennie HuiReedik MägiMaria DimitriouMelissa E GarciaWeang-kee HoMargaret J WrightLynda M RosePatrik Ke MagnussonMichael A NallsNancy L PedersenDavid CouperBen A OostraAlbert HofmanMohammad Arfan IkramHenning W TiemeierAndre G UitterlindenFrank Ja Van RooijInês BarrosoIngegerd JohanssonAndrea GannaLuting XueMarika KaakinenLili MilaniChris PowerHarold SniederRonald P StolkSebastian E BaumeisterReiner BiffarFangyi GuFrançois BastardotNina PaynterZoltán KutalikDavid R JacobsNita G ForouhiEvelin MihailovLars LindCecilia LindgrenKarl MichaëlssonAndrew MorrisMajken JensenKay-tee KhawKeri L MondaRobert N LubenJie Jin WangSatu MännistöMia-maria PeräläMika KähönenTerho LehtimäkiJorma ViikariDariush MozaffarianKenneth MukamalBruce M PsatyNajaf AminAngela DöringAndrew C HeathGrant W MontgomeryNorbert DahmenTeresa CarithersKatherine L TuckerLuigi FerrucciHeather A BoydMads MelbyeJorien L TreurKrista FischerD. MellströmJouke Jan HottengaInga ProkopenkoAnke TönjesPanos DeloukasStavroula KanoniMattias LorentzonDenise K HoustonYongmei LiuJohn Daneshsubject
INVOLVEMENTNetherlands Twin Register (NTR)GCKR protein humanPROTEINGenome-wide association studyVARIANTSgenetics [Brain-Derived Neurotrophic Factor]chemistry.chemical_compound0302 clinical medicinePolymorphism (computer science)genetics [Adaptor Proteins Signal Transducing]BINDINGBRAINGenetics0303 health sciencesBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsDisorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]3. Good healthPsychiatry and Mental healthPhenotypegenetics [Polymorphism Single Nucleotide]/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beinggenetics [Cytochrome P-450 CYP1A2]CaffeineCAFFEINESingle-nucleotide polymorphismBiologyArticle03 medical and health sciencesCellular and Molecular NeuroscienceSDG 3 - Good Health and Well-beingCytochrome P-450 CYP1A2/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_SNPHumansddc:610Allelegenetics [Basic Helix-Loop-Helix Leucine Zipper Transcription Factors]Molecular Biology030304 developmental biologyAdaptor Proteins Signal TransducingMLXIPL protein humanRECEPTORBrain-Derived Neurotrophic FactorCoffeata1182Feeding Behaviorbiology.organism_classificationta3124BDNFchemistryBehavioral medicineDevelopmental Psychopathology030217 neurology & neurosurgeryGLUCOKINASEmetabolism [Coffea]Genome-Wide Association Studydescription
Contains fulltext : 155360.pdf (Publisher’s version ) (Closed access) 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 x 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 | journal | country | edition | language |
|---|---|---|---|---|
| 2015-05-01 | Molecular Psychiatry |