Assessment of sex-specific genetic and environmental effects on bone mineral density

Although it is widely accepted that genes contribute significantly to the variation in bone mineral density (BMD), the nature of the genetic contribution is poorly defined. There are large gender differences in BMD, although whether sex-specific genetic effects influencing variation in BMD contribute to these differences is not known. To address this issue, we studied 929 subjects from large families participating in the Amish Family Osteoporosis Study. Bone mineral density was measured at the hip and spine by dual energy X-ray absorptiometry (DXA). We used variance decomposition procedures to partition variation in BMD into genetic and environmental effects common to both sexes and to men and women separately. After accounting for covariate effects, the heritability of BMD ranged from 0.63 to 0.72 in men and 0.80 to 0.87 in women. The residual environmental variance in BMD at the spine, but not hip, was significantly higher in men than in women (P < 0.05), reflecting a greater variance in BMD due to unexplained non-genetic factors in men. In contrast, there were no significant differences between men and women in the magnitude of the genetic variance in BMD, nor did the genetic correlation in BMD between men and women differ significantly from one. Overall, these analyses do not provide evidence for sex-specific genetic effects, suggesting that many of the genes influencing variation in BMD should be detectable in both men and women.