Linkage Study of Fibrinogen Levels: The Strong Heart Family Study
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Best, Lyle G, et al. Linkage Study of Fibrinogen Levels: The Strong Heart Family Study. BioMed Central Ltd, 2008. https://doi.org/10.17615/676k-qc54APA
Best, L., North, K., Li, X., Palmieri, V., Umans, J., Mac Cluer, J., Laston, S., Haack, K., Goring, H., Diego, V., Almasy, L., Lee, E., Tracy, R., & Cole, S. (2008). Linkage Study of Fibrinogen Levels: The Strong Heart Family Study. BioMed Central Ltd. https://doi.org/10.17615/676k-qc54Chicago
Best, Lyle G, Kari North, Xia Li, Vittorio Palmieri, Jason G Umans, Jean Mac Cluer, Sandy Laston et al. 2008. Linkage Study of Fibrinogen Levels: The Strong Heart Family Study. BioMed Central Ltd. https://doi.org/10.17615/676k-qc54- Creator
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Best, Lyle G
- Other Affiliation: Missouri Breaks Industries Research Inc, Timber Lake, SD, USA
- North, Kari
- Li, Xia
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Palmieri, Vittorio
- Other Affiliation: Weill Medical College of Cornell University, New York, NY, USA
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Umans, Jason G
- Other Affiliation: Medstar Research Institute, Washington, DC, USA
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MacCluer, Jean
- Other Affiliation: Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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Laston, Sandy
- Other Affiliation: Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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Haack, Karin
- Other Affiliation: Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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Goring, Harald
- Other Affiliation: Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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Diego, Vincent P
- Other Affiliation: Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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Almasy, Laura
- Other Affiliation: Southwest Foundation for Biomedical Research, San Antonio, TX, USA
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Lee, Elisa T
- Other Affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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Tracy, Russell P
- Other Affiliation: Laboratory for Clinical Biochemistry Research, University of Vermont, Burlington, Vermont, USA
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Cole, Shelley
- Other Affiliation: Southwest Foundation for Biomedical Research, San Antonio, TX, USA
- Abstract
- Abstract Background The pathogenesis of atherosclerosis involves both hemostatic and inflammatory mechanisms. Fibrinogen is associated with both risk of thrombosis and inflammation. A recent meta-analysis showed that risk of coronary heart disease may increase 1.8 fold for 1 g/L of increased fibrinogen, independent of traditional risk factors. It is known that fibrinogen levels may be influenced by demographic, environmental and genetic factors. Epidemiologic and candidate gene studies are available; but few genome-wide linkage studies have been conducted, particularly in minority populations. The Strong Heart Study has demonstrated an increased incidence of cardiovascular disease in the American Indian population, and therefore represents an important source for genetic-epidemiological investigations. Methods The Strong Heart Family Study enrolled over 3,600 American Indian participants in large, multi-generational families, ascertained from an ongoing population-based study in the same communities. Fibrinogen was determined using standard technique in a central laboratory and extensive additional phenotypic measures were obtained. Participants were genotyped for 382 short tandem repeat markers distributed throughout the genome; and results were analyzed using a variance decomposition method, as implemented in the SOLAR 2.0 program. Results Data from 3535 participants were included and after step-wise, linear regression analysis, two models were selected for investigation. Basic demographic adjustments constituted model 1, while model 2 considered waist circumference, diabetes mellitus and postmenopausal status as additional covariates. Five LOD scores between 1.82 and 3.02 were identified, with the maximally adjusted model showing the highest score on chromosome 7 at 28 cM. Genes for two key components of the inflammatory response, i.e. interleukin-6 and "signal transducer and activator of transcription 3" (STAT3), were identified within 2 and 8 Mb of this 1 LOD drop interval respectively. A LOD score of 1.82 on chromosome 17 between 68 and 93 cM is supported by reports from two other populations with LOD scores of 1.4 and 1.95. Conclusion In a minority population with a high prevalence of cardiovascular disease, strong evidence for a novel genetic determinant of fibrinogen levels is found on chromosome 7 at 28 cM. Four other loci, some of which have been suggested by previous studies, were also identified.
- Date of publication
- August 12, 2008
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- Lyle G Best et al.; licensee BioMed Central Ltd.
- License
- Journal title
- BMC Medical Genetics
- Journal volume
- 9
- Journal issue
- 1
- Page start
- 77
- Language
- English
- Is the article or chapter peer-reviewed?
- Yes
- ISSN
- 1471-2350
- Bibliographic citation
- BMC Medical Genetics. 2008 Aug 12;9(1):77
- Publisher
- BioMed Central Ltd
- Access right
- Open Access
- Date uploaded
- August 23, 2012
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