• Xiang-He Meng, Li-Jun Tan, Hong-Mei Xiao, Bei-Sha Tang, and Hong-Wen Deng.
• Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
• Bone. 2019 Aug 1; 125: 25-29.

AbstractLeptin, 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.Copyright © 2019 Elsevier Inc. All rights reserved.

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