Evidence of major gene control of cortical bone loss in humans

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 p roperties 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 hyp othesis of major gene control of CI variation in a large sample of pedigree s from Chuvashia, Russia. Complex segregation analysis revealed that the ma jor 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 c hanges (inflection point) and the rate of the CI decrease with age (slope c oefficient) are under control of the same major gene. Nonmajor gene effects shared by pedigree members (residual familial correlations) were found to be statistically insignificant. Approximately 73% of inter-individual varia tion in CI was attributable to the effects explicitly included in the model . (C) 2000 Wiley-Liss, Inc.