title: Prospective study of circulating factor XI and incident venous thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE).
abstract: Elevated plasma concentrations of coagulation factor XI may increase risk of venous thromboembolism (VTE), but prospective data are limited. We studied prospectively the associations of plasma factor XI and a key F11 genetic variant with incident VTE in whites and African-Americans. We measured factor XI in 16,299 participants, initially free of VTE, in two prospective population cohorts. We also measured the F11 single nucleotide polymorphism rs4241824, which a genome-wide association study had linked to factor XI concentration. During follow-up, we identified 606 VTEs. The age, race, sex, and study-adjusted hazard ratio of VTE increased across factor XI quintiles (P < 0.001 for trend), and the hazard ratio was 1.51 (95% CI 1.16, 1.97) for the highest versus lowest quintile overall, and was 1.42 (95% CI 1.03, 1.95) in whites and 1.72 (95% CI 1.08, 2.73) in African-Americans. In whites, the F11 variant was associated with both factor XI concentration and VTE incidence (1.15-fold greater incidence of VTE per risk allele). In African-Americans, these associations were absent. In conclusion, this cohort study documented that an elevated plasma factor XI concentration is a risk factor for VTE over extended follow-up, not only in whites but also in African-Americans. In whites, the association of the F11 genetic variant with VTE suggests a causal relation, but we did not observe this genetic relation in African-Americans.
authors.affiliation: Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.affiliation: Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Weihong
authors.initials: W
authors.lastname: Tang
authors.affiliation: Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Roetker
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: Department of Medicine, University of Vermont, Burlington, Vermont.|Department of Pathology, University of Vermont, Burlington, Vermont.
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
mesh_terms: D001741:Black or African American; D000368:Aged; D000483:Alleles; D005172:Factor XI / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D044465:White People
chemical_list: D005172:Factor XI