Site and gender specificity of inheritance of bone mineral density

Duncan, Emma L., Cardon, Lon R., Sinsheimer, Janet S., Wass, John A.H., & Brown, Matthew A. (2003) Site and gender specificity of inheritance of bone mineral density. Journal of Bone and Mineral Research, 18(8), pp. 1531-1538.

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Differences in genetic control of BMD by skeletal sites and genders were examined by complex segregation analysis in 816 members of 147 families with probands with extreme low BMD. Spine BMD correlated more strongly in male-male comparisons and hip BMD in female-female comparisons, consistent with gender- and site-specificity of BMD heritability.


Evidence from studies in animals and humans suggests that the genetic control of bone mineral density (BMD) may differ at different skeletal sites and between genders. This question has important implications for the design and interpretation of genetic studies of osteoporosis.


We examined the genetic profile of 147 families with 816 individuals recruited through probands with extreme low BMD (T-score < −2.5, Z-score < −2.0). Complex segregation analysis was performed using the Pedigree Analysis Package. BMD was measured by DXA at both lumbar spine (L1-L4) and femoral neck.


Complex segregation analysis excluded purely monogenic and environmental models of segregation of lumbar spine and femoral neck BMD in these families. Pure polygenic models were excluded at the lumbar spine when menopausal status was considered as a covariate, but not at the femoral neck. Mendelian models with a residual polygenic component were not excluded. These models were consistent with the presence of a rare Mendelian genotype of prevalence 3–19 %, causing high BMD at the hip and spine in these families, with additional polygenic effects. Total heritability range at the lumbar spine was 61–67 % and at the femoral neck was 44–67 %. Significant differences in correlation of femoral neck and lumbar spine BMD were observed between male and female relative pairs, with male-male comparisons exhibiting stronger lumbar spine BMD correlation than femoral neck, and female-female comparisons having greater femoral neck BMD correlation than lumbar spine. These findings remained true for parent-offspring correlations when menopausal status was taken into account. The recurrence risk ratio for siblings of probands of a Z-score < −2.0 was 5.4 at the lumbar spine and 5.9 at the femoral neck.


These findings support gender- and site-specificity of the inheritance of BMD. These results should be considered in the design and interpretation of genetic studies of osteoporosis.

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ID Code: 89548
Item Type: Journal Article
Refereed: Yes
Keywords: Bone density, Genetic, Heritability, Osteoporosis, Segregation, article, comparative study, controlled study, correlation analysis, dual energy X ray absorptiometry, environmental factor, extremely low bone mineral density, family, femur neck, gender, genetic analysis, genotype, hip, human, inheritance, lumbar spine, major clinical study, menopause, parent, pedigree analysis, phylogeny, prevalence, progeny, recurrence risk, scoring system, segregation analysis, sex difference, spine, statistical significance, theoretical model, female, genetics, lumbar vertebra, male, physiology, risk factor, sexual development, Humans, Lumbar Vertebrae, Risk Factors, Sex Characteristics
DOI: 10.1359/jbmr.2003.18.8.1531
ISSN: 0884-0431
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2003 Americal Society of Bone and Mineral Research
Deposited On: 27 Oct 2015 00:47
Last Modified: 28 Mar 2016 23:47

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