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Baumert, Jens; Huang, Jie; McKnight, Barbara; Sabater-Lleal, Maria; Steri, Maristella; Audrey Y. Chu; 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.; Brendan M Buckley; de Craen, Anton J. M.; Sanna, Serena; Masala, Marco; Biffar, Reiner; Homuth, Georg ... view all 103 authors View less authors (2014)
Publisher: Public Library of Science
Languages: English
Types: Article
Subjects: Myocardial infarction, INDIVIDUAL PARTICIPANT METAANALYSIS, 3121 Internal medicine, Genetic variation, Lung cancer, Clinical Genetics, Science, LOCI, Epidemiology, Medizin, CARDIOVASCULAR-DISEASE RISK, Q, R, Association, 515 Psychology, Cardiology, Research Article, MYOCARDIAL-INFARCTION, Hematology, CIRCULATING FIBRINOGEN, Cardiovascular disease risk, Medicine and Health Sciences, Inflammatory markers, Cigarette smoking, Loci, INFLAMMATORY MARKERS, Medicine, LUNG-CANCER, GENETIC-VARIATION, CIGARETTE-SMOKING, Circulating fibrinogen, Individual participant metaanalysis, ASSOCIATION
ddc: ddc:610
textabstractPlasma 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.

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Funded by projects

  • NIH | THE FRAMINGHAM HEART STUDY-...
  • WT
  • EC | GMI

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