Linkage study of fibrinogen levels

The Strong Heart Family Study

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Article number77
JournalBMC Medical Genetics
Volume9
DOIs
StatePublished - Aug 12 2008
Externally publishedYes

Fingerprint

Fibrinogen
Chromosomes, Human, Pair 7
North American Indians
Population
Cardiovascular Diseases
Demography
Genome
Social Adjustment
STAT3 Transcription Factor
Chromosomes, Human, Pair 17
Waist Circumference
Hemostatics
Microsatellite Repeats
Genes
Coronary Disease
Meta-Analysis
Linear Models
Interleukin-6
Atherosclerosis
Diabetes Mellitus

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)

Cite this

Best, L. G., North, K. E., Li, X., Palmieri, V., Umans, J. G., MacCluer, J., ... Cole, S. (2008). Linkage study of fibrinogen levels: The Strong Heart Family Study. BMC Medical Genetics, 9, [77]. https://doi.org/10.1186/1471-2350-9-77

Linkage study of fibrinogen levels : The Strong Heart Family Study. / Best, Lyle G.; North, Kari E.; Li, Xia; Palmieri, Vittorio; Umans, Jason G.; MacCluer, Jean; Laston, Sandy; Haack, Karin; Goring, Harald; Diego, Vincent P.; Almasy, Laura; Lee, Elisa T.; Tracy, Russell P.; Cole, Shelley.

In: BMC Medical Genetics, Vol. 9, 77, 12.08.2008.

Research output: Contribution to journalArticle

Best, LG, North, KE, Li, X, Palmieri, V, Umans, JG, MacCluer, J, Laston, S, Haack, K, Goring, H, Diego, VP, Almasy, L, Lee, ET, Tracy, RP & Cole, S 2008, 'Linkage study of fibrinogen levels: The Strong Heart Family Study', BMC Medical Genetics, vol. 9, 77. https://doi.org/10.1186/1471-2350-9-77
Best LG, North KE, Li X, Palmieri V, Umans JG, MacCluer J et al. Linkage study of fibrinogen levels: The Strong Heart Family Study. BMC Medical Genetics. 2008 Aug 12;9. 77. https://doi.org/10.1186/1471-2350-9-77
Best, Lyle G. ; North, Kari E. ; Li, Xia ; Palmieri, Vittorio ; Umans, Jason G. ; MacCluer, Jean ; Laston, Sandy ; Haack, Karin ; Goring, Harald ; Diego, Vincent P. ; Almasy, Laura ; Lee, Elisa T. ; Tracy, Russell P. ; Cole, Shelley. / Linkage study of fibrinogen levels : The Strong Heart Family Study. In: BMC Medical Genetics. 2008 ; Vol. 9.
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