title: Evidence for common controls over inheritance of bone quantity and body size from segregation analysis in a pedigreed colony of nonhuman primates (Macaca nemestrina).
abstract: The genetic determinants of bone mineral quantity and body size and their postulated interaction are just beginning to be elucidated. The heritability of bone quantity and its relationship to components of body size were therefore investigated using segregation analysis applied to a large pedigreed nonhuman primate (Macaca nemestrina) breeding colony. The colony consisted of 216 females and 16 males with uniform dietary histories, environmental conditions, and rearing of offspring apart from the mother to minimize familial aggregation. Bone quantity (bone mineral content and spinal areal density) was measured by dual-energy X-ray absorptiometry (DXA). Size included measures of body mass, length, breadth, and a composite index. Body mass was determined from both body weight and lean body mass by DXA. Length was assessed by measuring trunk and thigh lengths, and breadth by measuring chest circumference and bitrochanteric width. A composite index of size was also calculated from a linear function of trunk and thigh lengths, chest circumference and bitrochanteric width, and lean body mass. Traits of bone quantity and size were highly correlated (r = 0.56-0.96, p < 0.001). Significant (p < or = 0.03) univariate heritabilities were found for spine bone mineral density (SPBMD; h(2) = 0.66) and whole body bone mineral content (WBBMC; h(2) = 0.40) and size measures of length (trunk h(2) = 0.71, thigh h(2) = 0.65), breadth (bitrochanteric width h(2) = 0.31), lean body mass (LEAN; h(2) = 0.37), and the composite index of size (SIZE-PC, h(2) = 0.49) adjusted for demographic variables. The data were also subjected to an analysis of bivariate genetic correlations and factor analysis, both of which suggested a robust interaction between body size and bone quantity. Bivariate genetic correlations between body size and the bone quantities WBBMC, SBMD, and spine bone mineral content (SPBMC) were high (e.g., using LEAN as a measure of size, r = 0.57, 0.41, and 0.57, respectively). Factor analysis showed that 80% of the phenotypic and 72% of the genetic variances of all traits were accounted for by a single factor, suggesting common genetic controls operative over bone quantity and size.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA. ewl@u.washington.edu
authors.forename: E W
authors.initials: EW
authors.lastname: Lipkin
authors.forename: C A
authors.initials: CA
authors.lastname: Aumann
authors.forename: L L
authors.initials: LL
authors.lastname: Newell-Morris
mesh_terms: D015502:Absorptiometry, Photon; D000367:Age Factors; D000818:Animals; D001824:Body Constitution / Q000235:genetics; D015519:Bone Density / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D008254:Macaca nemestrina / Q000033:anatomy & histology*; D008297:Male; D010024:Osteoporosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013131:Spine / Q000033:anatomy & histology / Q000000981:diagnostic imaging