title: Univariate and bivariate variance component linkage analysis of a whole-genome scan for loci contributing to bone mineral density.
abstract: Osteoporosis is a common condition characterized by reduced skeletal strength and increased susceptibility to fracture. The single major risk factor for osteoporosis is low bone mineral density (BMD) and strong evidence exists that genetic factors are in part responsible for an individual's BMD. A cohort of 40 multiplex Caucasian families selected through a proband with osteoporosis was genotyped for microsatellite markers spaced at an average of 10 cM, and linkage to femoral neck (FN), lumbar spine (LS) and trochanter (TR) BMD was analyzed using univariate and bivariate variance component linkage analysis. Maximum univariate multipoint lod-scores were 2.87 on chromosome 1p36 for FN BMD, 1.89 on 6q27 for TR BMD, and 2.15 on 7p15 for LS BMD. Results of bivariate linkage analysis were highly correlated with those of the univariate analysis, although generally less significant, suggesting the possibility that some of these susceptibility loci may exert pleiotropic effects on multiple skeletal sites.
authors.affiliation: Department of Biomedical Research, Nemours Children's Clinic, Wilmington, DE, USA. mdevoto@nemours.org
authors.forename: Marcella
authors.initials: M
authors.lastname: Devoto
authors.forename: Loretta D
authors.initials: LD
authors.lastname: Spotila
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Stabley
authors.forename: Gina N
authors.initials: GN
authors.lastname: Wharton
authors.forename: Halfdan
authors.initials: H
authors.lastname: Rydbeck
authors.forename: Jarmo
authors.initials: J
authors.lastname: Korkko
authors.forename: Richard
authors.initials: R
authors.lastname: Kosich
authors.forename: Darwin
authors.initials: D
authors.lastname: Prockop
authors.forename: Alan
authors.initials: A
authors.lastname: Tenenhouse
authors.forename: Katia
authors.initials: K
authors.lastname: Sol-Church
mesh_terms: D000704:Analysis of Variance; D015519:Bone Density / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats; D015999:Multivariate Analysis; D010024:Osteoporosis / Q000235:genetics*; D010375:Pedigree; D040641:Quantitative Trait Loci; D012307:Risk Factors