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 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

doi:10.1371/journal.pone.0111156

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 journal › Article › peer-review

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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.

Original language	English (US)
Article number	e111156
Journal	PLoS One
Volume	9
Issue number	12
DOIs	https://doi.org/10.1371/journal.pone.0111156
State	Published - Dec 31 2014
Externally published	Yes

ASJC Scopus subject areas

General Agricultural and Biological Sciences
General Biochemistry, Genetics and Molecular Biology
General Medicine

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10.1371/journal.pone.0111156

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Baumert, J., Huang, J., McKnight, B., Sabater-Lleal, M., Steri, M., Chu, A. Y., Trompet, S., Lopez, L. M., Fornage, M., Teumer, A., Tang, W., Rudnicka, A. R., Mälarstig, A., Hottenga, J. J., Kavousi, M., Lahti, J., Tanaka, T., Hayward, C., Huffman, J. E., ... Smith, N. L. (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), Article e111156. https://doi.org/10.1371/journal.pone.0111156

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

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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",

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.",

author = "Jens Baumert and Jie Huang and Barbara McKnight and Maria Sabater-Lleal and Maristella Steri and Chu, {Audrey Y.} and Stella Trompet and Lopez, {Lorna M.} and Myriam Fornage and Alexander Teumer and Weihong Tang and Rudnicka, {Alicja R.} and Anders M{\"a}larstig and Hottenga, {Jouke Jan} and Maryam Kavousi and Jari Lahti and Toshiko Tanaka and Caroline Hayward and Huffman, {Jennifer E.} and Morange, {Pierre Emmanuel} and Rose, {Lynda M.} and Saonli Basu and Ann Rumley and Stott, {David J.} and Buckley, {Brendan M.} and {De Craen}, {Anton J M} and Serena Sanna and Marco Masala and Reiner Biffar and Georg Homuth and Angela Silveira and Bengt Sennblad and Anuj Goel and Hugh Watkins and Martina M{\"u}ller-Nurasyid and Regina R{\"u}ckerl and Kent Taylor and Chen, {Ming Huei} and {De Geus}, {Eco J C} and Albert Hofman and Witteman, {Jacqueline C M} and {De Maat}, {Moniek P M} and Aarno Palotie and Gail Davies and Siscovick, {David S.} and Ivana Kolcic and Wild, {Sarah H.} and Jaejoon Song and McArdle, {Wendy L.} and Ian Ford and Naveed Sattar and David Schlessinger and Anne Grotevendt and Franzosi, {Maria Grazia} and Thomas Illig and Melanie Waldenberger and Thomas Lumley and Tofler, {Geoffrey H.} and Gonneke Willemsen and Uitterlinden, {Andr{\'e} G.} and Fernando Rivadeneira and Katri R{\"a}ikk{\"o}nen and Chasman, {Daniel I.} and Folsom, {Aaron R.} and Lowe, {Gordon D.} and Westendorp, {Rudi G J} and Slagboom, {P. Eline} and Francesco Cucca and Henri Wallaschofski and Strawbridge, {Rona J.} and Udo Seedorf and Wolfgang Koenig and Bis, {Joshua C.} and Mukamal, {Kenneth J.} and {Van Dongen}, Jenny and Elisabeth Widen and Franco, {Oscar H.} and Starr, {John M.} and Kiang Liu and Luigi Ferrucci and Ozren Polasek and Wilson, {James F.} and Tiphaine Oudot-Mellakh and Harry Campbell and Pau Navarro and Stefania Bandinelli and Johan Eriksson and Boomsma, {Dorret I.} and Abbas Dehghan and Robert Clarke and Anders Hamsten and Eric Boerwinkle and Jukema, {J. Wouter} and Silvia Naitza and Ridker, {Paul M.} and Henry V{\"o}lzke and Deary, {Ian J.} and Reiner, {Alexander P.} and Tr{\'e}gou{\"e}t, {David Alexandre} and O'Donnell, {Christopher J.} and Strachan, {David P.} and Annette Peters and Smith, {Nicholas L.}",

year = "2014",

month = dec,

day = "31",

doi = "10.1371/journal.pone.0111156",

language = "English (US)",

volume = "9",

journal = "PLoS One",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "12",

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TY - JOUR

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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U2 - 10.1371/journal.pone.0111156

DO - 10.1371/journal.pone.0111156

M3 - Article

C2 - 25551457

AN - SCOPUS:84938634406

SN - 1932-6203

VL - 9

JO - PLoS One

JF - PLoS One

IS - 12

M1 - e111156

ER -

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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