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.

 
TitleNo evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.
Publication TypeJournal Article
Year of Publication2014
AuthorsBaumert, 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, J-J, Kavousi, M, Lahti, J, Tanaka, T, Hayward, C, Huffman, JE, Morange, P-E, 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, M-H, 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, MGrazia, Illig, T, Waldenberger, M, Lumley, T, Tofler, GH, Willemsen, G, Uitterlinden, AG, Rivadeneira, F, Räikkönen, K, Chasman, DI, Folsom, AR, Lowe, GD, Westendorp, RGJ, P Slagboom, E, 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, J Jukema, W, Naitza, S, Ridker, PM, Völzke, H, Deary, IJ, Reiner, AP, Trégouët, D-A, O'Donnell, CJ, Strachan, DP, Peters, A, Smith, NL
JournalPLoS One
Volume9
Issue12
Paginatione111156
Date Published2014
ISSN1932-6203
KeywordsAlcohol Drinking, Body Mass Index, Fibrinogen, Gene-Environment Interaction, Genomics, Humans, Smoking
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.

DOI10.1371/journal.pone.0111156
Alternate JournalPLoS ONE
PubMed ID25551457
PubMed Central IDPMC4281156
Grant ListCZB/4/710 / / Chief Scientist Office / United Kingdom
N01-HC-25195 / HC / NHLBI NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States