INTRODUCTION: Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. MATERIALS AND METHODS: We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. RESULTS AND DISCUSSIONS: The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD=1.5 at 243 cM) and 10 (LOD=2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD=2.1 at 242 cM) and 10(LOD=1.4 at 86 cM), 17 (LOD=1.4 at 96 cM) and 20 (LOD=1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted.
INTRODUCTION: Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. MATERIALS AND METHODS: We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. RESULTS AND DISCUSSIONS: The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD=1.5 at 243 cM) and 10 (LOD=2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD=2.1 at 242 cM) and 10(LOD=1.4 at 86 cM), 17 (LOD=1.4 at 96 cM) and 20 (LOD=1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted.
Authors: Cara L Carty; Patrick Heagerty; Susan R Heckbert; Gail P Jarvik; Leslie A Lange; Mary Cushman; Russell P Tracy; Alexander P Reiner Journal: Ann Hum Genet Date: 2010-01 Impact factor: 1.670
Authors: Lyle G Best; Kari E North; Xia Li; Vittorio Palmieri; Jason G Umans; Jean MacCluer; Sandy Laston; Karin Haack; Harald Goring; Vincent P Diego; Laura Almasy; Elisa T Lee; Russell P Tracy; Shelley Cole Journal: BMC Med Genet Date: 2008-08-12 Impact factor: 2.103
Authors: Dilyara G Yanbaeva; Mieke A Dentener; Martijn A Spruit; Jeanine J Houwing-Duistermaat; Daniel Kotz; Valéria Lima Passos; Emiel F M Wouters Journal: BMC Med Genet Date: 2009-03-09 Impact factor: 2.103
Authors: Abbas Dehghan; Qiong Yang; Annette Peters; Saonli Basu; Joshua C Bis; Alicja R Rudnicka; Maryam Kavousi; Ming-Huei Chen; Jens Baumert; Gordon D O Lowe; Barbara McKnight; Weihong Tang; Moniek de Maat; Martin G Larson; Susana Eyhermendy; Wendy L McArdle; Thomas Lumley; James S Pankow; Albert Hofman; Joseph M Massaro; Fernando Rivadeneira; Melanie Kolz; Kent D Taylor; Cornelia M van Duijn; Sekar Kathiresan; Thomas Illig; Yurii S Aulchenko; Kelly A Volcik; Andrew D Johnson; Andre G Uitterlinden; Geoffrey H Tofler; Christian Gieger; Bruce M Psaty; David J Couper; Eric Boerwinkle; Wolfgang Koenig; Christopher J O'Donnell; Jacqueline C Witteman; David P Strachan; Nicholas L Smith; Aaron R Folsom Journal: Circ Cardiovasc Genet Date: 2009-04