Age at menarche and osteoporosis: A Mendelian randomization study
Qiang Zhang1, Jonathan Greenbaum2, Wei-Dong Zhang1
1College of Public Health, Zhengzhou University, Zhengzhou, NO.100 Kexue Road, High-Tech Development Zone Of States, PR China.
Bone
|September 22, 2018
Summary
Later age at menarche (AAM) is causally linked to reduced bone mineral density (BMD), increasing osteoporosis risk. This Mendelian randomization study confirms AAM
Area of Science:
- Genetics
- Epidemiology
- Bone Biology
Background:
- Epidemiological studies suggest an association between age at menarche (AAM) and bone mineral density (BMD).
- Potential confounding factors may obscure the true relationship between AAM and BMD.
- Understanding this relationship is crucial for osteoporosis (OP) etiology.
Purpose of the Study:
- To determine the causal relationship between AAM and BMD at the femoral neck (FNK) and lumbar spine (LS).
- To investigate if later AAM increases the risk of developing OP.
Main Methods:
- Employed a two-sample Mendelian randomization (MR) approach.
- Utilized genome-wide association study (GWAS) summary statistics from the ReproGen and GEFOS Consortia.
- Analyzed data from 182,416 females (ReproGen) and 53,236 individuals (GEFOS).
Main Results:
- Each additional year in AAM was associated with a modest reduction in FNK BMD (β = -0.072, p = 0.001).
- Each additional year in AAM was associated with a modest reduction in LS BMD (β = -0.072, p = 0.004).
- These findings indicate that AAM influences OP susceptibility.
Conclusions:
- Age at menarche plays a causal role in osteoporosis etiology in females.
- Provides novel insights into the pathophysiology of bone-related diseases such as osteoporosis, osteopenia, and fracture.
- MR approach mitigates bias from unmeasured confounders and reverse causation.
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