title: Evidence for a genetic link between bone and vascular measures in African ancestry families.
abstract: Bone mineral density (BMD) has been inversely associated with subclinical and clinical cardiovascular disease (CVD) in population studies, but the potential mechanisms underlying this relationship are unclear. To test if there is a genetic basis underlying this association, we determined the phenotypic and genetic correlations between BMD and carotid artery ultrasound measures in families. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were used to measure BMD in 461 individuals with African ancestry belonging to seven large, multigenerational families (mean family size 66; 3414 total relative pairs). Carotid artery ultrasound was used to measure adventitial diameter (AD) and intima-media thickness (IMT). Phenotypic and genetic correlations between BMD and carotid measures were determined using pedigree-based maximum likelihood methods. We adjusted for potential confounding factors, including age, sex, body weight, height, menopausal status, smoking, alcohol intake, walking for exercise, diabetes, hypertension, serum lipid and lipoprotein levels, inflammation markers, and kidney function. We found statistically significant phenotypic (ρ = -0.19) and genetic (ρG  = -0.70) correlations (p < 0.05 for both) between lumbar spine BMD and AD in fully adjusted models. There was also a significant genetic correlation between trabecular BMD at the radius and IMT in fully adjusted models (ρG  = -0.398; p < 0.05). Our findings indicate that the previously observed association between osteoporosis and CVD in population-based studies may be partly mediated by genetic factors and that the pleiotropic effects of these genes may operate independently of traditional risk pathways.
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15261, USA. kuipers@pitt.edu
authors.forename: Allison L
authors.initials: AL
authors.lastname: Kuipers
authors.forename: Iva
authors.initials: I
authors.lastname: Miljkovic
authors.forename: Candace M
authors.initials: CM
authors.lastname: Kammerer
authors.forename: Rhobert W
authors.initials: RW
authors.lastname: Evans
authors.forename: Clareann H
authors.initials: CH
authors.lastname: Bunker
authors.forename: Alan L
authors.initials: AL
authors.lastname: Patrick
authors.forename: Victor W
authors.initials: VW
authors.lastname: Wheeler
authors.forename: Kim
authors.initials: K
authors.lastname: Sutton-Tyrrell
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zmuda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics*; D015519:Bone Density / Q000235:genetics; D002339:Carotid Arteries / Q000473:pathology* / Q000503:physiopathology; D005190:Family; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008159:Lumbar Vertebrae / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D015999:Multivariate Analysis; D010024:Osteoporosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012307:Risk Factors; D055815:Young Adult
keywords: ADVENTITIAL DIAMETER; AFRICAN ANCESTRY; BONE MINERAL DENSITY; GENETIC CORRELATION; INTIMA-MEDIA THICKNESS