Brown Lillian B, Streeten Elizabeth A, Shuldiner Alan R, Almasy Laura A, Peyser Patricia A, Mitchell Braxton D
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan 21201, USA.
Genet Epidemiol. 2004 Sep;27(2):153-61. doi: 10.1002/gepi.20009.
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.
尽管人们普遍认为基因对骨矿物质密度（BMD）的变异有显著贡献，但基因贡献的本质却定义不清。BMD存在很大的性别差异，不过影响BMD变异的性别特异性遗传效应是否导致了这些差异尚不清楚。为了解决这个问题，我们研究了参与阿米什家族骨质疏松症研究的大家庭中的929名受试者。通过双能X线吸收法（DXA）测量髋部和脊柱的骨矿物质密度。我们使用方差分解程序将BMD的变异分为男女共有的遗传和环境效应以及男性和女性各自的遗传和环境效应。在考虑协变量效应后，男性BMD的遗传率在0.63至0.72之间，女性在0.80至0.87之间。男性脊柱（而非髋部）BMD的残余环境方差显著高于女性（P < 0.05），这反映出男性中由无法解释的非遗传因素导致的BMD方差更大。相比之下，男性和女性在BMD遗传方差的大小上没有显著差异，男性和女性之间BMD的遗传相关性也与1没有显著差异。总体而言，这些分析没有提供性别特异性遗传效应的证据，这表明许多影响BMD变异的基因在男性和女性中都应该是可检测到的。
