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Quantitative genetics of circulating molecules associated with bone metabolism: a review
1Human Population Biology Research Unit, Department of Anatomy and Anthropology, and Yoran Institute for Human Genome Research, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. gregl@post.tau.ac.il
Summary
Genetic factors significantly influence bone metabolism biomarkers, with heritability up to 80%. Understanding these genetic links is crucial for identifying new targets in bone disease research.
Area of Science:
- Biochemistry
- Genetics
- Bone Metabolism
Background:
- Bone metabolism involves complex interactions between hormones, cytokines, and growth factors.
- Interindividual variation in biomarker levels is influenced by familial and genetic effects.
Purpose of the Study:
- To review recent advances in biochemical factors (biomarkers) of bone metabolism.
- To summarize genetic influences on biomarker variation and co-variation.
- To highlight the need for further molecular genetic studies.
Main Methods:
- Literature review of studies on bone metabolism biomarkers.
- Analysis of heritability estimates for circulating biomarker levels.
- Examination of genetic correlations between biomarker variations.
- Brief consideration of gene expression and microarray data.
Main Results:
- Heritability estimates for many biomarkers exceed 20%, reaching up to 80% for some cytokines.
- Limited pleiotropic effects observed despite strong genetic influences on individual biomarkers.
- Significant genetic correlations found only in specific biomarker pairs (e.g., IGF-I/IGFBP-3).
Conclusions:
- Genetic factors play a substantial role in bone metabolism biomarker variation.
- Identifying specific genes affecting biomarker levels and co-variation is imperative.
- Bone metabolism is an open system, modulated by external factors like PTH.
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