No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects

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dc.contributor.authorBaumert, Jens
dc.contributor.authorHuang, Jie
dc.contributor.authorMcKnight, Barbara
dc.contributor.authorSabater-Lleal, Maria
dc.contributor.authorSteri, Maristella
dc.contributor.authorChu, Audrey Y.
dc.contributor.authorTrompet, Stella
dc.contributor.authorLopez, Lorna M.
dc.contributor.authorFornage, Myriam
dc.contributor.authorTeumer, Alexander
dc.contributor.authorTang, Weihong
dc.contributor.authorRudnicka, Alicja R.
dc.contributor.authorMaelarstig, Anders
dc.contributor.authorHottenga, Jouke-Jan
dc.contributor.authorKavousi, Maryam
dc.contributor.authorLahti, Jari
dc.contributor.authorTanaka, Toshiko
dc.contributor.authorHayward, Caroline
dc.contributor.authorHuffman, Jennifer E.
dc.contributor.authorMorange, Pierre-Emmanuel
dc.contributor.authorRose, Lynda M.
dc.contributor.authorBasu, Saonli
dc.contributor.authorRumley, Ann
dc.contributor.authorStott, David J.
dc.contributor.authorBuckley, Brendan M.
dc.contributor.authorde Craen, Anton J. M.
dc.contributor.authorSanna, Serena
dc.contributor.authorMasala, Marco
dc.contributor.authorBiffar, Reiner
dc.contributor.authorHomuth, Georg
dc.contributor.authorSilveira, Angela
dc.contributor.authorSennblad, Bengt
dc.contributor.authorGoel, Anuj
dc.contributor.authorWatkins, Hugh
dc.contributor.authorMueller-Nurasyid, Martina
dc.contributor.authorRueckerl, Regina
dc.contributor.authorTaylor, Kent
dc.contributor.authorChen, Ming-Huei
dc.contributor.authorde Geus, Eco J. C.
dc.contributor.authorHofman, Albert
dc.contributor.authorWitteman, Jacqueline C. M.
dc.contributor.authorde Maat, Moniek P. M.
dc.contributor.authorPalotie, Aarno
dc.contributor.authorDavies, Gail
dc.contributor.authorSiscovick, David S.
dc.contributor.authorKolcic, Ivana
dc.contributor.authorWild, Sarah H.
dc.contributor.authorSong, Jaejoon
dc.contributor.authorMcArdle, Wendy L.
dc.contributor.authorFord, Ian
dc.contributor.authorSattar, Naveed
dc.contributor.authorSchlessinger, David
dc.contributor.authorGrotevendt, Anne
dc.contributor.authorFranzosi, Maria Grazia
dc.contributor.authorIllig, Thomas
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorLumley, Thomas
dc.contributor.authorTofler, Geoffrey H.
dc.contributor.authorWillemsen, Gonneke
dc.contributor.authorUitterlinden, Andre G.
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorRäikkönen, Katri
dc.contributor.authorChasman, Daniel I.
dc.contributor.authorFolsom, Aaron R.
dc.contributor.authorLowe, Gordon D.
dc.contributor.authorWestendorp, Rudi G. J.
dc.contributor.authorSlagboom, P. Eline
dc.contributor.authorCucca, Francesco
dc.contributor.authorWallaschofski, Henri
dc.contributor.authorStrawbridge, Rona J.
dc.contributor.authorSeedorf, Udo
dc.contributor.authorKoenig, Wolfgang
dc.contributor.authorBis, Joshua C.
dc.contributor.authorMukamal, Kenneth J.
dc.contributor.authorvan Dongen, Jenny
dc.contributor.authorWiden, Elisabeth
dc.contributor.authorFranco, Oscar H.
dc.contributor.authorStarr, John M.
dc.contributor.authorLiu, Kiang
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorPolasek, Ozren
dc.contributor.authorWilson, James F.
dc.contributor.authorOudot-Mellakh, Tiphaine
dc.contributor.authorCampbell, Harry
dc.contributor.authorNavarro, Pau
dc.contributor.authorBandinelli, Stefania
dc.contributor.authorEriksson, Johan
dc.contributor.authorBoomsma, Dorret I.
dc.contributor.authorDehghan, Abbas
dc.contributor.authorClarke, Robert
dc.contributor.authorHamsten, Anders
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorJukema, J. Wouter
dc.contributor.authorNaitza, Silvia
dc.contributor.authorRidker, Paul M.
dc.contributor.authorVoezke, Henry
dc.contributor.authorDeary, Ian J.
dc.contributor.authorReiner, Alexander P.
dc.contributor.authorTregoueet, David-Alexandre
dc.contributor.authorO'Donnell, Christopher J.
dc.contributor.authorStrachan, David P.
dc.contributor.authorPeters, Annette
dc.contributor.authorSmith, Nicholas L.
dc.contributor.funderNational Heart, Lung and Blood Institute
dc.contributor.funderAffymetrix Inc.
dc.contributor.funderBristol-Myers Squibb
dc.contributor.funderAXA Research Fund
dc.contributor.funderNestlé Nutrition
dc.contributor.funderMetagenics Inc.
dc.contributor.funderSiemens Healthcare
dc.contributor.funderFederal State of Mecklenburg
dc.date.accessioned2016-02-17T11:43:37Z
dc.date.available2016-02-17T11:43:37Z
dc.date.issued2014
dc.description.abstractPlasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2x10(-8). This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.en
dc.description.sponsorshipNational Heart, Lung and Blood Institute, United States (Framingham Heart Study N01-HC-25195); Affymetrix, Inc, United States (N02-HL-6-4278)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide111156
dc.identifier.citationBaumert J, Huang J, McKnight B, Sabater-Lleal M, Steri M, Chu AY, et al. (2014) No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index: Results from Meta-Analyses of 80,607 Subjects. PLoS ONE 9(12): e111156. doi:10.1371/journal.pone.0111156
dc.identifier.doi10.1371/journal.pone.0111156
dc.identifier.issn1932-6203
dc.identifier.issued12en
dc.identifier.journaltitlePLOS ONEen
dc.identifier.urihttps://hdl.handle.net/10468/2317
dc.identifier.volume9en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.rights© 2015 Baumert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectIndividual participant metaanalysisen
dc.subjectCardiovascular disease risken
dc.subjectCirculating fibrinogenen
dc.subjectMyocardial infarctionen
dc.subjectLung canceren
dc.subjectInflammatory markersen
dc.subjectCigarette smokingen
dc.subjectGenetic variationen
dc.subjectAssociationen
dc.subjectLocien
dc.titleNo evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjectsen
dc.typeArticle (peer-reviewed)en
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