title: Genetic analysis of serum osteocalcin and bone mineral in multigenerational Afro-Caribbean families.
abstract: Osteocalcin is a major component of bone matrix. Concentrations of total, carboxylated, and uncarboxylated osteocalcin, are highly heritable and genetically correlated with bone mineral content (BMC) within African ancestry families.
  
  
  BACKGROUND
  Osteocalcin (OC) is a protein constituent of bone matrix and a marker of bone formation. We characterized the heritability of serum OC measures and identified genomic regions potentially involved in the regulation of OC via high-density genome-wide linkage analysis in African ancestry individuals.
  
  
  METHODS
  African ancestry individuals (n = 459) were recruited, without regard to health status, from seven probands (mean family size = 66; 4,373 relative pairs). Residual heritability of serum OC measures was estimated and multipoint quantitative trait linkage analysis was performed using pedigree-based maximum likelihood methods.
  
  
  RESULTS
  Residual heritabilities of total OC, uncarboxylated OC, carboxylated OC and percent uncarboxylated OC were 0.74 ± 0.10, 0.89 ± 0.08, 0.46 ± 0.10 and 0.41 ± 0.09, respectively. All OC measures were genetically correlated with whole body BMC. We obtained strong evidence of bivariate linkage for percent uncarboxylated OC and whole body BMC on chromosome 17 (logarithm of the odds [LOD] = 3.15, 99 cM).
  
  
  CONCLUSIONS
  All forms of OC were highly heritable and genetically correlated with total body BMC in these African ancestry families. The identified linkage region contains several candidate genes for bone and energy metabolism including COL1A1 and TNFRSF11A. Further studies of this genomic region may reveal novel insight into the genetic regulation of OC and bone mineralization.
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15261, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Kuipers
authors.forename: C
authors.initials: C
authors.lastname: Gundberg
authors.forename: C M
authors.initials: CM
authors.lastname: Kammerer
authors.forename: A S
authors.initials: AS
authors.lastname: Dressen
authors.forename: C S
authors.initials: CS
authors.lastname: Nestlerode
authors.forename: A L
authors.initials: AL
authors.lastname: Patrick
authors.forename: V W
authors.initials: VW
authors.lastname: Wheeler
authors.forename: C H
authors.initials: CH
authors.lastname: Bunker
authors.forename: A B
authors.initials: AB
authors.lastname: Newman
authors.forename: J M
authors.initials: JM
authors.lastname: Zmuda
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics*; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood / Q000235:genetics*; D040641:Quantitative Trait Loci; D055815:Young Adult
chemical_list: D015675:Osteocalcin