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.

Plasma 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 pla...

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Main Authors: Jens Baumert, Jie Huang, Barbara McKnight, Maria Sabater-Lleal, Maristella Steri, Audrey Y Chu, Stella Trompet, Lorna M Lopez, Myriam Fornage, Alexander Teumer, Weihong Tang, Alicja R Rudnicka, Anders Mälarstig, Jouke-Jan Hottenga, Maryam Kavousi, Jari Lahti, Toshiko Tanaka, Caroline Hayward, Jennifer E Huffman, Pierre-Emmanuel Morange, Lynda M Rose, Saonli Basu, Ann Rumley, David J Stott, Brendan M Buckley, Anton J M de Craen, Serena Sanna, Marco Masala, Reiner Biffar, Georg Homuth, Angela Silveira, Bengt Sennblad, Anuj Goel, Hugh Watkins, Martina Müller-Nurasyid, Regina Rückerl, Kent Taylor, Ming-Huei Chen, Eco J C de Geus, Albert Hofman, Jacqueline C M Witteman, Moniek P M de Maat, Aarno Palotie, Gail Davies, David S Siscovick, Ivana Kolcic, Sarah H Wild, Jaejoon Song, Wendy L McArdle, Ian Ford, Naveed Sattar, David Schlessinger, Anne Grotevendt, Maria Grazia Franzosi, Thomas Illig, Melanie Waldenberger, Thomas Lumley, Geoffrey H Tofler, Gonneke Willemsen, André G Uitterlinden, Fernando Rivadeneira, Katri Räikkönen, Daniel I Chasman, Aaron R Folsom, Gordon D Lowe, Rudi G J Westendorp, P Eline Slagboom, Francesco Cucca, Henri Wallaschofski, Rona J Strawbridge, Udo Seedorf, Wolfgang Koenig, Joshua C Bis, Kenneth J Mukamal, Jenny van Dongen, Elisabeth Widen, Oscar H Franco, John M Starr, Kiang Liu, Luigi Ferrucci, Ozren Polasek, James F Wilson, Tiphaine Oudot-Mellakh, Harry Campbell, Pau Navarro, Stefania Bandinelli, Johan Eriksson, Dorret I Boomsma, Abbas Dehghan, Robert Clarke, Anders Hamsten, Eric Boerwinkle, J Wouter Jukema, Silvia Naitza, Paul M Ridker, Henry Völzke, Ian J Deary, Alexander P Reiner, David-Alexandre Trégouët, Christopher J O'Donnell, David P Strachan, Annette Peters, Nicholas L Smith
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Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0111156
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_version_ 1850162097235689472
author Jens Baumert
Jie Huang
Barbara McKnight
Maria Sabater-Lleal
Maristella Steri
Audrey Y Chu
Stella Trompet
Lorna M Lopez
Myriam Fornage
Alexander Teumer
Weihong Tang
Alicja R Rudnicka
Anders Mälarstig
Jouke-Jan Hottenga
Maryam Kavousi
Jari Lahti
Toshiko Tanaka
Caroline Hayward
Jennifer E Huffman
Pierre-Emmanuel Morange
Lynda M Rose
Saonli Basu
Ann Rumley
David J Stott
Brendan M Buckley
Anton J M de Craen
Serena Sanna
Marco Masala
Reiner Biffar
Georg Homuth
Angela Silveira
Bengt Sennblad
Anuj Goel
Hugh Watkins
Martina Müller-Nurasyid
Regina Rückerl
Kent Taylor
Ming-Huei Chen
Eco J C de Geus
Albert Hofman
Jacqueline C M Witteman
Moniek P M de Maat
Aarno Palotie
Gail Davies
David S Siscovick
Ivana Kolcic
Sarah H Wild
Jaejoon Song
Wendy L McArdle
Ian Ford
Naveed Sattar
David Schlessinger
Anne Grotevendt
Maria Grazia Franzosi
Thomas Illig
Melanie Waldenberger
Thomas Lumley
Geoffrey H Tofler
Gonneke Willemsen
André G Uitterlinden
Fernando Rivadeneira
Katri Räikkönen
Daniel I Chasman
Aaron R Folsom
Gordon D Lowe
Rudi G J Westendorp
P Eline Slagboom
Francesco Cucca
Henri Wallaschofski
Rona J Strawbridge
Udo Seedorf
Wolfgang Koenig
Joshua C Bis
Kenneth J Mukamal
Jenny van Dongen
Elisabeth Widen
Oscar H Franco
John M Starr
Kiang Liu
Luigi Ferrucci
Ozren Polasek
James F Wilson
Tiphaine Oudot-Mellakh
Harry Campbell
Pau Navarro
Stefania Bandinelli
Johan Eriksson
Dorret I Boomsma
Abbas Dehghan
Robert Clarke
Anders Hamsten
Eric Boerwinkle
J Wouter Jukema
Silvia Naitza
Paul M Ridker
Henry Völzke
Ian J Deary
Alexander P Reiner
David-Alexandre Trégouët
Christopher J O'Donnell
David P Strachan
Annette Peters
Nicholas L Smith
author_facet Jens Baumert
Jie Huang
Barbara McKnight
Maria Sabater-Lleal
Maristella Steri
Audrey Y Chu
Stella Trompet
Lorna M Lopez
Myriam Fornage
Alexander Teumer
Weihong Tang
Alicja R Rudnicka
Anders Mälarstig
Jouke-Jan Hottenga
Maryam Kavousi
Jari Lahti
Toshiko Tanaka
Caroline Hayward
Jennifer E Huffman
Pierre-Emmanuel Morange
Lynda M Rose
Saonli Basu
Ann Rumley
David J Stott
Brendan M Buckley
Anton J M de Craen
Serena Sanna
Marco Masala
Reiner Biffar
Georg Homuth
Angela Silveira
Bengt Sennblad
Anuj Goel
Hugh Watkins
Martina Müller-Nurasyid
Regina Rückerl
Kent Taylor
Ming-Huei Chen
Eco J C de Geus
Albert Hofman
Jacqueline C M Witteman
Moniek P M de Maat
Aarno Palotie
Gail Davies
David S Siscovick
Ivana Kolcic
Sarah H Wild
Jaejoon Song
Wendy L McArdle
Ian Ford
Naveed Sattar
David Schlessinger
Anne Grotevendt
Maria Grazia Franzosi
Thomas Illig
Melanie Waldenberger
Thomas Lumley
Geoffrey H Tofler
Gonneke Willemsen
André G Uitterlinden
Fernando Rivadeneira
Katri Räikkönen
Daniel I Chasman
Aaron R Folsom
Gordon D Lowe
Rudi G J Westendorp
P Eline Slagboom
Francesco Cucca
Henri Wallaschofski
Rona J Strawbridge
Udo Seedorf
Wolfgang Koenig
Joshua C Bis
Kenneth J Mukamal
Jenny van Dongen
Elisabeth Widen
Oscar H Franco
John M Starr
Kiang Liu
Luigi Ferrucci
Ozren Polasek
James F Wilson
Tiphaine Oudot-Mellakh
Harry Campbell
Pau Navarro
Stefania Bandinelli
Johan Eriksson
Dorret I Boomsma
Abbas Dehghan
Robert Clarke
Anders Hamsten
Eric Boerwinkle
J Wouter Jukema
Silvia Naitza
Paul M Ridker
Henry Völzke
Ian J Deary
Alexander P Reiner
David-Alexandre Trégouët
Christopher J O'Donnell
David P Strachan
Annette Peters
Nicholas L Smith
author_sort Jens Baumert
collection DOAJ
description Plasma 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 6.2 × 10(-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.
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spelling doaj-art-2a5482c6a0714ca39c607dfcc7abcd702025-08-20T02:22:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11115610.1371/journal.pone.0111156No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.Jens BaumertJie HuangBarbara McKnightMaria Sabater-LlealMaristella SteriAudrey Y ChuStella TrompetLorna M LopezMyriam FornageAlexander TeumerWeihong TangAlicja R RudnickaAnders MälarstigJouke-Jan HottengaMaryam KavousiJari LahtiToshiko TanakaCaroline HaywardJennifer E HuffmanPierre-Emmanuel MorangeLynda M RoseSaonli BasuAnn RumleyDavid J StottBrendan M BuckleyAnton J M de CraenSerena SannaMarco MasalaReiner BiffarGeorg HomuthAngela SilveiraBengt SennbladAnuj GoelHugh WatkinsMartina Müller-NurasyidRegina RückerlKent TaylorMing-Huei ChenEco J C de GeusAlbert HofmanJacqueline C M WittemanMoniek P M de MaatAarno PalotieGail DaviesDavid S SiscovickIvana KolcicSarah H WildJaejoon SongWendy L McArdleIan FordNaveed SattarDavid SchlessingerAnne GrotevendtMaria Grazia FranzosiThomas IlligMelanie WaldenbergerThomas LumleyGeoffrey H ToflerGonneke WillemsenAndré G UitterlindenFernando RivadeneiraKatri RäikkönenDaniel I ChasmanAaron R FolsomGordon D LoweRudi G J WestendorpP Eline SlagboomFrancesco CuccaHenri WallaschofskiRona J StrawbridgeUdo SeedorfWolfgang KoenigJoshua C BisKenneth J MukamalJenny van DongenElisabeth WidenOscar H FrancoJohn M StarrKiang LiuLuigi FerrucciOzren PolasekJames F WilsonTiphaine Oudot-MellakhHarry CampbellPau NavarroStefania BandinelliJohan ErikssonDorret I BoomsmaAbbas DehghanRobert ClarkeAnders HamstenEric BoerwinkleJ Wouter JukemaSilvia NaitzaPaul M RidkerHenry VölzkeIan J DearyAlexander P ReinerDavid-Alexandre TrégouëtChristopher J O'DonnellDavid P StrachanAnnette PetersNicholas L SmithPlasma 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 6.2 × 10(-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.https://doi.org/10.1371/journal.pone.0111156
spellingShingle Jens Baumert
Jie Huang
Barbara McKnight
Maria Sabater-Lleal
Maristella Steri
Audrey Y Chu
Stella Trompet
Lorna M Lopez
Myriam Fornage
Alexander Teumer
Weihong Tang
Alicja R Rudnicka
Anders Mälarstig
Jouke-Jan Hottenga
Maryam Kavousi
Jari Lahti
Toshiko Tanaka
Caroline Hayward
Jennifer E Huffman
Pierre-Emmanuel Morange
Lynda M Rose
Saonli Basu
Ann Rumley
David J Stott
Brendan M Buckley
Anton J M de Craen
Serena Sanna
Marco Masala
Reiner Biffar
Georg Homuth
Angela Silveira
Bengt Sennblad
Anuj Goel
Hugh Watkins
Martina Müller-Nurasyid
Regina Rückerl
Kent Taylor
Ming-Huei Chen
Eco J C de Geus
Albert Hofman
Jacqueline C M Witteman
Moniek P M de Maat
Aarno Palotie
Gail Davies
David S Siscovick
Ivana Kolcic
Sarah H Wild
Jaejoon Song
Wendy L McArdle
Ian Ford
Naveed Sattar
David Schlessinger
Anne Grotevendt
Maria Grazia Franzosi
Thomas Illig
Melanie Waldenberger
Thomas Lumley
Geoffrey H Tofler
Gonneke Willemsen
André G Uitterlinden
Fernando Rivadeneira
Katri Räikkönen
Daniel I Chasman
Aaron R Folsom
Gordon D Lowe
Rudi G J Westendorp
P Eline Slagboom
Francesco Cucca
Henri Wallaschofski
Rona J Strawbridge
Udo Seedorf
Wolfgang Koenig
Joshua C Bis
Kenneth J Mukamal
Jenny van Dongen
Elisabeth Widen
Oscar H Franco
John M Starr
Kiang Liu
Luigi Ferrucci
Ozren Polasek
James F Wilson
Tiphaine Oudot-Mellakh
Harry Campbell
Pau Navarro
Stefania Bandinelli
Johan Eriksson
Dorret I Boomsma
Abbas Dehghan
Robert Clarke
Anders Hamsten
Eric Boerwinkle
J Wouter Jukema
Silvia Naitza
Paul M Ridker
Henry Völzke
Ian J Deary
Alexander P Reiner
David-Alexandre Trégouët
Christopher J O'Donnell
David P Strachan
Annette Peters
Nicholas L Smith
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
title 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.
title_full 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.
title_fullStr 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.
title_full_unstemmed 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.
title_short 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.
title_sort 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
url https://doi.org/10.1371/journal.pone.0111156
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AT kiangliu noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT luigiferrucci noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT ozrenpolasek noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT jamesfwilson noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT tiphaineoudotmellakh noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT harrycampbell noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT paunavarro noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT stefaniabandinelli noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT johaneriksson noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT dorretiboomsma noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT abbasdehghan noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT robertclarke noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT andershamsten noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT ericboerwinkle noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT jwouterjukema noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT silvianaitza noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT paulmridker noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT henryvolzke noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT ianjdeary noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT alexanderpreiner noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT davidalexandretregouet noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT christopherjodonnell noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT davidpstrachan noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT annettepeters noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects
AT nicholaslsmith noevidenceforgenomewideinteractionsonplasmafibrinogenbysmokingalcoholconsumptionandbodymassindexresultsfrommetaanalysesof80607subjects