Meyre, David and Baumert, Jens and Huang, Jie and McKnight, Barbara and Sabater-Lleal, Maria and Steri, Maristella and Chu, Audrey Y. and Trompet, Stella and Lopez, Lorna M. and Fornage, Myriam and Teumer, Alexander and Tang, Weihong and Rudnicka, Alicja R. and Mälarstig, Anders and Hottenga, Jouke-Jan and Kavousi, Maryam and Lahti, Jari and Tanaka, Toshiko and Hayward, Caroline and Huffman, Jennifer E. and Morange, Pierre-Emmanuel and Rose, Lynda M. and Basu, Saonli and Rumley, Ann and Stott, David J. and Buckley, Brendan M. and de Craen, Anton J. M. and Sanna, Serena and Masala, Marco and Biffar, Reiner and Homuth, Georg and Silveira, Angela and Sennblad, Bengt and Goel, Anuj and Watkins, Hugh and Müller-Nurasyid, Martina and Rückerl, Regina and Taylor, Kent and Chen, Ming-Huei and de Geus, Eco J. C. and Hofman, Albert and Witteman, Jacqueline C. M. and de Maat, Moniek P. M. and Palotie, Aarno and Davies, Gail and Siscovick, David S. and Kolcic, Ivana and Wild, Sarah H. and Song, Jaejoon and McArdle, Wendy L. and Ford, Ian and Sattar, Naveed and Schlessinger, David and Grotevendt, Anne and Franzosi, Maria Grazia and Illig, Thomas and Waldenberger, Melanie and Lumley, Thomas and Tofler, Geoffrey H. and Willemsen, Gonneke and Uitterlinden, André G. and Rivadeneira, Fernando and Räikkönen, Katri and Chasman, Daniel I. and Folsom, Aaron R. and Lowe, Gordon D. and Westendorp, Rudi G. J. and Slagboom, P. Eline and Cucca, Francesco and Wallaschofski, Henri and Strawbridge, Rona J. and Seedorf, Udo and Koenig, Wolfgang and Bis, Joshua C. and Mukamal, Kenneth J. and van Dongen, Jenny and Widen, Elisabeth and Franco, Oscar H. and Starr, John M. and Liu, Kiang and Ferrucci, Luigi and Polasek, Ozren and Wilson, James F. and Oudot-Mellakh, Tiphaine and Campbell, Harry and Navarro, Pau and Bandinelli, Stefania and Eriksson, Johan and Boomsma, Dorret I. and Dehghan, Abbas and Clarke, Robert and Hamsten, Anders and Boerwinkle, Eric and Jukema, J. Wouter and Naitza, Silvia and Ridker, Paul M. and Völzke, Henry and Deary, Ian J. and Reiner, Alexander P. and Trégouët, David-Alexandre and O'Donnell, Christopher J. and Strachan, David P. and Peters, Annette and Smith, Nicholas 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). e111156. ISSN 1932-6203

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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.

Item Type:	Article
Keywords:	Evidence; Genome-Wide; Interactions; Plasma Fibrinogen; Smoking, Alcohol Consumption; Body Mass Index; BMI; Results; Meta-Analyses; 80,607 Subjects;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17248
Identification Number:	https://doi.org/10.1371/journal.pone.0111156
Depositing User:	Lorna Lopez
Date Deposited:	29 May 2023 14:52
Journal or Publication Title:	PLoS ONE
Publisher:	Public Library of Science
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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