Identifying Genes Affecting Bone Mineral Density and Fracture Risk
Author Information
Author(s): Duncan Emma L., Danoy Patrick, Kemp John P., Leo Paul J., McCloskey Eugene, Nicholson Geoffrey C., Eastell Richard, Prince Richard L., Eisman John A., Jones Graeme, Sambrook Philip N., Reid Ian R., Dennison Elaine M., Wark John, Richards J. Brent, Uitterlinden Andre G., Spector Tim D., Esapa Chris, Cox Roger D., Brown Steve D. M., Thakker Rajesh V., Addison Kathryn A., Bradbury Linda A., Center Jacqueline R., Cooper Cyrus, Cremin Catherine, Estrada Karol, Felsenberg Dieter, Glüer Claus-C., Hadler Johanna, Henry Margaret J., Hofman Albert, Kotowicz Mark A., Makovey Joanna, Nguyen Sing C., Nguyen Tuan V., Pasco Julie A., Pryce Karena, Reid David M., Rivadeneira Fernando, Roux Christian, Stefansson Kari, Styrkarsdottir Unnur, Thorleifsson Gudmar, Tichawangana Rumbidzai, Evans David M., Brown Matthew A.
Primary Institution: University of Queensland Diamantina Institute
Hypothesis
Can a genome-wide association study identify novel genes associated with bone mineral density and fracture risk in postmenopausal women?
Conclusion
The study identified six new genetic associations with bone mineral density and confirmed the efficiency of extreme-truncate selection designs for such studies.
Supporting Evidence
- The study replicated 21 of 26 known BMD-associated genes.
- Six new genetic associations were identified in or around specific genes.
- A novel mouse model with a GALNT3 mutation showed high bone mass.
- The study design focused on a high-risk demographic to improve power.
- Findings were confirmed in a large cohort of women from the general population.
- Extreme-truncate selection designs were shown to be efficient for quantitative trait studies.
Takeaway
Researchers looked at women with very high or very low bone density to find new genes that affect bone health. They found some new genes and confirmed many known ones.
Methodology
The study used a genome-wide association study design focusing on postmenopausal women with extreme bone mineral density.
Potential Biases
Potential bias due to the selection of participants based on extreme bone mineral density.
Limitations
The study focused only on postmenopausal women, which may limit the generalizability of the findings to other populations.
Participant Demographics
Postmenopausal women aged 55-85 years, primarily of self-reported white European ancestry.
Statistical Information
P-Value
p<5×10−8
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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