College of Public Health, Zhengzhou University, Zhengzhou, NO.100 Kexue Road, High-Tech Development Zone Of States, PR China.
Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
Bone. 2018 Dec;117:91-97. doi: 10.1016/j.bone.2018.09.015. Epub 2018 Sep 18.
Traditional epidemiological studies suggest that there is an association between age at menarche (years) (AAM) and bone mineral density (BMD) at the sites of the femoral neck and lumbar spine (FNK and LS BMD), indicating a potentially important relationship between AAM and the development of osteoporosis (OP). However, these findings may be influenced by unmeasured confounding factors that can obscure the true relationship between the phenotypic traits. Therefore, we performed Mendelian randomization (MR) analyses to determine whether there is a causal relationship between AAM and BMD (FNK and LS BMD), where late AAM may increase the risk of developing OP.
Adopting a two-sample MR approach we incorporated genome-wide association (GWAS) summary statistics from the Reproductive Genetics (ReproGen) Consortium (n = 182,416) (females only) and the GEnetic Factors for OSteoporosis (GEFOS) Consortium (n = 53,236) (both males and females).
Using this MR approach we discovered that each additional year in AAM is associated with a modest reduction in FNK BMD (β = -0.072 se = 0.022, 95% CI (-0.115, -0.030), p = 0.001) and LS BMD ((β = -0.072, se = 0.025, 95% CI (-0.121, -0.023), p = 0.004), and therefore influences OP susceptibility.
This study demonstrates that AAM in females may play a causal role in OP etiology and provides novel insights into the pathophysiology of bone related diseases like osteoporosis, osteopenia and fracture.
Our study demonstrates that AAM in females may play a causal role in OP etiology and provides novel insights into the pathophysiology of bone related diseases like osteoporosis, osteopenia and fracture. By adopting Mendelian Randomization approaches, our study was not susceptible to bias from unmeasured confounders or reverse causation.
传统的流行病学研究表明，初潮年龄（岁）（AAM）与股骨颈和腰椎骨密度（FNK 和 LS BMD）之间存在关联，表明 AAM 与骨质疏松症（OP）的发展之间存在潜在的重要关系。然而，这些发现可能受到无法测量的混杂因素的影响，这些因素可能会掩盖表型特征之间的真实关系。因此，我们进行了孟德尔随机化（MR）分析，以确定 AAM 与 BMD（FNK 和 LS BMD）之间是否存在因果关系，其中晚 AAM 可能会增加发生 OP 的风险。
采用两样本 MR 方法，我们纳入了生殖遗传学（ReproGen）联盟（n=182416）（仅女性）和基因因素骨质疏松症（GEFOS）联盟（n=53236）（男性和女性）的全基因组关联（GWAS）汇总统计数据。
使用这种 MR 方法，我们发现 AAM 每增加一年，股骨颈 BMD（β=-0.072 se=0.022，95%CI（-0.115，-0.030），p=0.001）和 LS BMD（β=-0.072，se=0.025，95%CI（-0.121，-0.023），p=0.004）都会略有下降，因此会影响 OP 的易感性。
本研究表明，女性的 AAM 可能在 OP 的病因学中起因果作用，并为骨质疏松症、低骨量和骨折等与骨骼相关疾病的病理生理学提供了新的见解。
本研究表明，女性的 AAM 可能在 OP 的病因学中起因果作用，并为骨质疏松症、低骨量和骨折等与骨骼相关疾病的病理生理学提供了新的见解。通过采用孟德尔随机化方法，我们的研究不受未测量混杂因素或反向因果关系的影响。
