Examining the causal role of leptin in bone mineral density: A Mendelian randomization study
Examining the causal role of leptin in bone mineral density: A Mendelian randomization study
复制标题
检查瘦素对骨矿物质密度的因果作用：孟德尔随机研究
DOI：
10.1016/j.bone.2019.05.006
复制
发表时间：
2019-08-01
期刊：
影响因子：
4.1
通讯作者：
Deng, Hong-Wen
中科院分区：
文献类型：
--
作者：
Meng, Xiang-He;Tan, Li-Jun;Deng, Hong-Wen
瘦素是一种由脂肪细胞分泌的小分子多肽激素，通过与位于下丘脑的特殊受体结合来控制体重和性腺功能。观察性研究表明瘦素与骨密度（BMD）之间存在争议，瘦素与BMD之间关系的功能研究仍然存在很大差异。使用52，140名个体中与瘦素水平密切相关的SNPs，我们进行了一项双样本孟德尔随机化研究，通过使用逆方差加权法，加权中位数法，MR-Egger和Robust Adjusted Profile Score来确定遗传性降低的瘦素水平是否与BMD相关。我们发现循环中的瘦素水平可能会导致腰椎BMD的降低（效应量=-0.45，95%CI：-0.82，-0.083; p值= 0.016）。瘦素水平与股骨颈、前臂和全身骨密度的相关性不显著。我们的研究表明，遗传预测较高的循环瘦素与较低的LS-BMD相关。
Leptin, a small polypeptide hormone secreted by the adipocytes, controls body weight and gonadal function by binding to a special receptor located in the hypothalamus. Observational studies have demonstrated a controversial association between leptin and bone mineral density (BMD), and functional studies of the relationship between leptin and BMD still largely vary by different studies. Using SNPs strongly associated with leptin levels in 52,140 individuals, we conducted a two-sample Mendelian randomization study to identify whether genetically lowered leptin levels were associated with BMD by using an inverse-variance weighted method, a weighted median method, MR-Egger and Robust Adjusted Profile Score. We found that circulating leptin levels may causally decrease lumbar spine BMD (effect size = -0.45, 95% CI: -0.82, -0.083; p value = 0.016). The association estimates of circulating leptin levels on femoral neck, forearm and total body BMD were not significant. Our study suggests that genetically predicted higher circulating leptin was associated with lower LS-BMD.