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:	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.
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281156/

id	pubmed-4281156
recordtype	oai_dc
spelling	pubmed-42811562015-01-07 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. Research Article 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. Public Library of Science 2014-12-31 /pmc/articles/PMC4281156/ /pubmed/25551457 http://dx.doi.org/10.1371/journal.pone.0111156 Text en © 2014 Baumert et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	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.
spellingShingle	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
author_facet	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.
author_sort	Baumert, Jens
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_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_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_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
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.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281156/
_version_	1613172298039164928

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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