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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posted on 2014-12-31, 03:20 authored by 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

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.