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Causal relationship between the AHSG gene and BMD through fetuin-A and BMI: multiple mediation analysis
C Sritara1, A Thakkinstian, B Ongphiphadhanakul
1Department of Diagnostic and Therapeutic Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, chanika.sri@mahidol.edu.
Summary
The AHSG gene influences bone mineral density (BMD) through fetuin-A and body mass index (BMI). This study suggests a causal link, explaining a significant portion of genetic effects on BMD.
Area of Science:
- Genetics
- Bone Metabolism
- Biochemistry
Background:
- Fetuin-A, a protein produced by the liver, is linked to bone mineral density (BMD).
- The exact nature of the association between fetuin-A and BMD remains unclear.
- This research investigates a potential causal relationship.
Purpose of the Study:
- To clarify the causal relationship between the AHSG gene and BMD.
- To examine the mediating roles of fetuin-A and body mass index (BMI) in this relationship.
Main Methods:
- A cross-sectional study of 1,741 healthy workers.
- Genotyping of the AHSG rs2248690 gene.
- Mediation analysis using seemingly unrelated regression to assess AHSG, fetuin-A, BMI, and BMD relationships, adjusted for confounders.
Main Results:
- The AHSG gene was strongly associated with serum fetuin-A levels.
- Mediation analysis revealed that AHSG significantly impacts BMD through fetuin-A and BMI.
- Fetuin-A and BMI mediated 27.3% and 26.0% of the genetic effects on hip and spine BMD, respectively.
Conclusions:
- The study provides evidence for a causal relationship between the AHSG gene and BMD.
- Fetuin-A and BMI act as significant mediators in the genetic pathway influencing BMD.
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