Evidence of major gene control of cortical bone loss in humans

Abstract

Cortical index (CI) is the ratio of the combined cortical thickness to the total diameter of the bone. It serves for the assessment of the geometric properties of bone and for indirect evaluation of bone mass. CI is a useful predictor of osteoporosis. The aim of the present study was to test the hypothesis of major gene control of CI variation in a large sample of pedigrees from Chuvashia, Russia. Complex segregation analysis revealed that the major gene model of CI inheritance is the best fitting and most parsimonious for the present data. Parameters of the genotype‐gender specific dependence of CI variation on age were estimated simultaneously with other parameters in the segregation analysis. The results of analysis showed that not only the baseline level of CI but also the age at onset of the involutive bone changes (inflection point) and the rate of the CI decrease with age (slope coefficient) are under control of the same major gene. Non‐major gene effects shared by pedigree members (residual familial correlations) were found to be statistically insignificant. Approximately 73% of inter‐individual variation in CI was attributable to the effects explicitly included in the model. Genet. Epidemiol. 19:410–421, 2000. © 2000 Wiley‐Liss, Inc.

Evidence for a major gene for bone mineral density/content in human pedigrees identified via probands with extreme bone mineral density

“…It is similar to the few segregation analyses performed earlier in randomly ascertained pedigrees from two ethnically different populations from the former Soviet Union (Livshits et al 1996 and in idiopathic osteoporotic families from New Zealand (Cardon et al 2000). Moreover, the pattern of genotype-i-sex-i-age interaction inferred in the present study is quite reminiscent of the results of a similar study by Livshits et al (2001) on hand digit BMD, and of Karasik et al (2000) who examined metacarpal cortical index inheritance. Yet, another segregation study (Gueguen et al 1995) did not support the existence of a major gene for BMD\BMC variation.…”

Proximal hip geometry is linked to several chromosomal regions: Genome-wide linkage results from the Framingham Osteoporosis Study

“…While it is well known that BMD is highly heritable [18,19], bone size and architecture are also under strong genetic influence [20]. Both men and women with a maternal history of osteoporosis have been shown to have thinner femoral cortices [21].…”

Quantitative genetics of cortical bone mass in healthy 10-year-old children from the Fels Longitudinal Study

“…Adult bone mass, primarily measured as bone mineral density (BMD), has typically been the focal phenotype in genetic studies of bone regulation in humans [6,8,9,18,29,[38][39][40]. With the growing awareness of the importance of childhood bone accrual in determining adult bone health status, however, genetic studies are emerging that incorporate children into the study design.…”

“…Radiographic cortical bone thickness is a well-recognized valuable method for assessing bone biology, and has long been used as a measure of skeletal mass [4,10,12,15,16,29,30,39,40,42]. Cortical thickness is measured as the amount of bone tissue present between the periosteal and endosteal surfaces.…”

“…Cortical measurements taken on a cylindrical bone such as the second metacarpal are generally more reliable than those taken from other bones [15]. Additionally, measures of cortical bone are less affected by shortterm temporal fluctuation in bone mass caused by seasonal variation and weight changes than measures of bone mineral density or bone mineral content obtained from dual energy x-ray absorptiometry [29].…”