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.
Highlights
Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade and is strongly associated with a variety of environmental factors such as smoking status, alcohol consumption or obesity [1,2,3,4,5,6,7]
The present study confirmed these associations and is in line with findings from a large meta-analysis of 154,211 participants in 31 prospective studies conducted by the Fibrinogen Studies Collaboration (FSC) which showed comparable estimates of fibrinogen concentration differences in smokers compared to non-smokers and for differences in body mass index (BMI) and alcohol consumption amounts [7]
The present study found no evidence that the strong associations of smoking status, alcohol consumption and BMI with fibrinogen concentrations were significantly modified by any of the approximately 2.6 million polymorphisms identified in the HapMap II Caucasian (CEU) sample
Summary
Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade and is strongly associated with a variety of environmental factors such as smoking status, alcohol consumption or obesity [1,2,3,4,5,6,7]. Elevated fibrinogen concentrations indicate increased risks for developing cardiovascular diseases [8,9,10]. Knowledge about potential interactions between environmental factors such as cardiovascular risk factors and gene variants on fibrinogen is still limited. A large meta-analysis showed elevated fibrinogen concentrations in current smokers compared with nonsmokers; fibrinogen concentrations increased with the number of cigarettes smoked per day showing a dose-related trend [7]. All three factors represent behavioral risk factors which are easy to assess and for which we hypothesized that gene-environment interactions may modify individual risks enabling potentially targeted and individualized preventive approaches
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
