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

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 MorangeLynda 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

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article numbere111156
JournalPLoS One
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 31 2014

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fibrinogen
Beam plasma interactions
Alcohol Drinking
Fibrinogen
body mass index
Meta-Analysis
Body Mass Index
Genes
Smoking
Alcohols
Genome
Plasmas
genome
single nucleotide polymorphism
Single Nucleotide Polymorphism
Polymorphism
Nucleotides
Chromosomes
risk factors
chromosomes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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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. / Baumert, Jens; Huang, Jie; McKnight, Barbara; Sabater-Lleal, Maria; Steri, Maristella; Chu, Audrey Y.; Trompet, Stella; Lopez, Lorna M.; Fornage, Myriam; Teumer, Alexander; Tang, Weihong; Rudnicka, Alicja R.; Mälarstig, Anders; Hottenga, Jouke Jan; Kavousi, Maryam; Lahti, Jari; Tanaka, Toshiko; Hayward, Caroline; Huffman, Jennifer E.; Morange, Pierre Emmanuel; Rose, Lynda M.; Basu, Saonli; Rumley, Ann; Stott, David J.; Buckley, Brendan M.; De Craen, Anton J M; Sanna, Serena; Masala, Marco; Biffar, Reiner; Homuth, Georg; Silveira, Angela; Sennblad, Bengt; Goel, Anuj; Watkins, Hugh; Müller-Nurasyid, Martina; Rückerl, Regina; Taylor, Kent; Chen, Ming Huei; De Geus, Eco J C; Hofman, Albert; Witteman, Jacqueline C M; De Maat, Moniek P M; Palotie, Aarno; Davies, Gail; Siscovick, David S.; Kolcic, Ivana; Wild, Sarah H.; Song, Jaejoon; McArdle, Wendy L.; Ford, Ian; Sattar, Naveed; Schlessinger, David; Grotevendt, Anne; Franzosi, Maria Grazia; Illig, Thomas; Waldenberger, Melanie; Lumley, Thomas; Tofler, Geoffrey H.; Willemsen, Gonneke; Uitterlinden, André G.; Rivadeneira, Fernando; Räikkönen, Katri; Chasman, Daniel I.; Folsom, Aaron R.; Lowe, Gordon D.; Westendorp, Rudi G J; Slagboom, P. Eline; Cucca, Francesco; Wallaschofski, Henri; Strawbridge, Rona J.; Seedorf, Udo; Koenig, Wolfgang; Bis, Joshua C.; Mukamal, Kenneth J.; Van Dongen, Jenny; Widen, Elisabeth; Franco, Oscar H.; Starr, John M.; Liu, Kiang; Ferrucci, Luigi; Polasek, Ozren; Wilson, James F.; Oudot-Mellakh, Tiphaine; Campbell, Harry; Navarro, Pau; Bandinelli, Stefania; Eriksson, Johan; Boomsma, Dorret I.; Dehghan, Abbas; Clarke, Robert; Hamsten, Anders; Boerwinkle, Eric; Jukema, J. Wouter; Naitza, Silvia; Ridker, Paul M.; Völzke, Henry; Deary, Ian J.; Reiner, Alexander P.; Trégouët, David Alexandre; O'Donnell, Christopher J.; Strachan, David P.; Peters, Annette; Smith, Nicholas L.

In: PLoS One, Vol. 9, No. 12, e111156, 31.12.2014.

Research output: Contribution to journalArticle

Baumert, J, Huang, J, McKnight, B, Sabater-Lleal, M, Steri, M, Chu, AY, Trompet, S, Lopez, LM, Fornage, M, Teumer, A, Tang, W, Rudnicka, AR, Mälarstig, A, Hottenga, JJ, Kavousi, M, Lahti, J, Tanaka, T, Hayward, C, Huffman, JE, Morange, PE, Rose, LM, Basu, S, Rumley, A, Stott, DJ, Buckley, BM, De Craen, AJM, Sanna, S, Masala, M, Biffar, R, Homuth, G, Silveira, A, Sennblad, B, Goel, A, Watkins, H, Müller-Nurasyid, M, Rückerl, R, Taylor, K, Chen, MH, De Geus, EJC, Hofman, A, Witteman, JCM, De Maat, MPM, Palotie, A, Davies, G, Siscovick, DS, Kolcic, I, Wild, SH, Song, J, McArdle, WL, Ford, I, Sattar, N, Schlessinger, D, Grotevendt, A, Franzosi, MG, Illig, T, Waldenberger, M, Lumley, T, Tofler, GH, Willemsen, G, Uitterlinden, AG, Rivadeneira, F, Räikkönen, K, Chasman, DI, Folsom, AR, Lowe, GD, Westendorp, RGJ, Slagboom, PE, Cucca, F, Wallaschofski, H, Strawbridge, RJ, Seedorf, U, Koenig, W, Bis, JC, Mukamal, KJ, Van Dongen, J, Widen, E, Franco, OH, Starr, JM, Liu, K, Ferrucci, L, Polasek, O, Wilson, JF, Oudot-Mellakh, T, Campbell, H, Navarro, P, Bandinelli, S, Eriksson, J, Boomsma, DI, Dehghan, A, Clarke, R, Hamsten, A, Boerwinkle, E, Jukema, JW, Naitza, S, Ridker, PM, Völzke, H, Deary, IJ, Reiner, AP, Trégouët, DA, O'Donnell, CJ, Strachan, DP, Peters, A & Smith, NL 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, vol. 9, no. 12, e111156. https://doi.org/10.1371/journal.pone.0111156
Baumert, Jens ; Huang, Jie ; McKnight, Barbara ; Sabater-Lleal, Maria ; Steri, Maristella ; Chu, Audrey Y. ; Trompet, Stella ; Lopez, Lorna M. ; Fornage, Myriam ; Teumer, Alexander ; Tang, Weihong ; Rudnicka, Alicja R. ; Mälarstig, Anders ; Hottenga, Jouke Jan ; Kavousi, Maryam ; Lahti, Jari ; Tanaka, Toshiko ; Hayward, Caroline ; Huffman, Jennifer E. ; Morange, Pierre Emmanuel ; Rose, Lynda M. ; Basu, Saonli ; Rumley, Ann ; Stott, David J. ; Buckley, Brendan M. ; De Craen, Anton J M ; Sanna, Serena ; Masala, Marco ; Biffar, Reiner ; Homuth, Georg ; Silveira, Angela ; Sennblad, Bengt ; Goel, Anuj ; Watkins, Hugh ; Müller-Nurasyid, Martina ; Rückerl, Regina ; Taylor, Kent ; Chen, Ming Huei ; De Geus, Eco J C ; Hofman, Albert ; Witteman, Jacqueline C M ; De Maat, Moniek P M ; Palotie, Aarno ; Davies, Gail ; Siscovick, David S. ; Kolcic, Ivana ; Wild, Sarah H. ; Song, Jaejoon ; McArdle, Wendy L. ; Ford, Ian ; Sattar, Naveed ; Schlessinger, David ; Grotevendt, Anne ; Franzosi, Maria Grazia ; Illig, Thomas ; Waldenberger, Melanie ; Lumley, Thomas ; Tofler, Geoffrey H. ; Willemsen, Gonneke ; Uitterlinden, André G. ; Rivadeneira, Fernando ; Räikkönen, Katri ; Chasman, Daniel I. ; Folsom, Aaron R. ; Lowe, Gordon D. ; Westendorp, Rudi G J ; Slagboom, P. Eline ; Cucca, Francesco ; Wallaschofski, Henri ; Strawbridge, Rona J. ; Seedorf, Udo ; Koenig, Wolfgang ; Bis, Joshua C. ; Mukamal, Kenneth J. ; Van Dongen, Jenny ; Widen, Elisabeth ; Franco, Oscar H. ; Starr, John M. ; Liu, Kiang ; Ferrucci, Luigi ; Polasek, Ozren ; Wilson, James F. ; Oudot-Mellakh, Tiphaine ; Campbell, Harry ; Navarro, Pau ; Bandinelli, Stefania ; Eriksson, Johan ; Boomsma, Dorret I. ; Dehghan, Abbas ; Clarke, Robert ; Hamsten, Anders ; Boerwinkle, Eric ; Jukema, J. Wouter ; Naitza, Silvia ; Ridker, Paul M. ; Völzke, Henry ; Deary, Ian J. ; Reiner, Alexander P. ; Trégouët, David Alexandre ; O'Donnell, Christopher J. ; Strachan, David P. ; Peters, Annette ; Smith, Nicholas L. / 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. In: PLoS One. 2014 ; Vol. 9, No. 12.
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abstract = "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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T1 - No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index

T2 - Results from meta-analyses of 80,607 subjects

AU - Baumert, Jens

AU - Huang, Jie

AU - McKnight, Barbara

AU - Sabater-Lleal, Maria

AU - Steri, Maristella

AU - Chu, Audrey Y.

AU - Trompet, Stella

AU - Lopez, Lorna M.

AU - Fornage, Myriam

AU - Teumer, Alexander

AU - Tang, Weihong

AU - Rudnicka, Alicja R.

AU - Mälarstig, Anders

AU - Hottenga, Jouke Jan

AU - Kavousi, Maryam

AU - Lahti, Jari

AU - Tanaka, Toshiko

AU - Hayward, Caroline

AU - Huffman, Jennifer E.

AU - Morange, Pierre Emmanuel

AU - Rose, Lynda M.

AU - Basu, Saonli

AU - Rumley, Ann

AU - Stott, David J.

AU - Buckley, Brendan M.

AU - De Craen, Anton J M

AU - Sanna, Serena

AU - Masala, Marco

AU - Biffar, Reiner

AU - Homuth, Georg

AU - Silveira, Angela

AU - Sennblad, Bengt

AU - Goel, Anuj

AU - Watkins, Hugh

AU - Müller-Nurasyid, Martina

AU - Rückerl, Regina

AU - Taylor, Kent

AU - Chen, Ming Huei

AU - De Geus, Eco J C

AU - Hofman, Albert

AU - Witteman, Jacqueline C M

AU - De Maat, Moniek P M

AU - Palotie, Aarno

AU - Davies, Gail

AU - Siscovick, David S.

AU - Kolcic, Ivana

AU - Wild, Sarah H.

AU - Song, Jaejoon

AU - McArdle, Wendy L.

AU - Ford, Ian

AU - Sattar, Naveed

AU - Schlessinger, David

AU - Grotevendt, Anne

AU - Franzosi, Maria Grazia

AU - Illig, Thomas

AU - Waldenberger, Melanie

AU - Lumley, Thomas

AU - Tofler, Geoffrey H.

AU - Willemsen, Gonneke

AU - Uitterlinden, André G.

AU - Rivadeneira, Fernando

AU - Räikkönen, Katri

AU - Chasman, Daniel I.

AU - Folsom, Aaron R.

AU - Lowe, Gordon D.

AU - Westendorp, Rudi G J

AU - Slagboom, P. Eline

AU - Cucca, Francesco

AU - Wallaschofski, Henri

AU - Strawbridge, Rona J.

AU - Seedorf, Udo

AU - Koenig, Wolfgang

AU - Bis, Joshua C.

AU - Mukamal, Kenneth J.

AU - Van Dongen, Jenny

AU - Widen, Elisabeth

AU - Franco, Oscar H.

AU - Starr, John M.

AU - Liu, Kiang

AU - Ferrucci, Luigi

AU - Polasek, Ozren

AU - Wilson, James F.

AU - Oudot-Mellakh, Tiphaine

AU - Campbell, Harry

AU - Navarro, Pau

AU - Bandinelli, Stefania

AU - Eriksson, Johan

AU - Boomsma, Dorret I.

AU - Dehghan, Abbas

AU - Clarke, Robert

AU - Hamsten, Anders

AU - Boerwinkle, Eric

AU - Jukema, J. Wouter

AU - Naitza, Silvia

AU - Ridker, Paul M.

AU - Völzke, Henry

AU - Deary, Ian J.

AU - Reiner, Alexander P.

AU - Trégouët, David Alexandre

AU - O'Donnell, Christopher J.

AU - Strachan, David P.

AU - Peters, Annette

AU - Smith, Nicholas L.

PY - 2014/12/31

Y1 - 2014/12/31

N2 - 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.

AB - 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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