Type 2 Diabetes Is Causally Associated With Reduced Serum Osteocalcin: A Genomewide Association and Mendelian Randomization Study

作者：Hailuan Zeng, Jieyu Ge, Wenjie Xu, Hui Ma, Lingyan Chen, Mingfeng Xia, Baishen Pan, Huandong Lin, Sijia Wang, Xin Gao · 发表于：Journal of Bone and Mineral Research · 年份：2020 · DOI：10.1002/jbmr.4330 · 被引用次数：42 · 研究领域：Genetic Associations and Epidemiology、Growth Hormone and Insulin-like Growth Factors、Genetic Syndromes and Imprinting

Recent advances indicate that bone and energy metabolism are closely related. However, little direct evidence on causality has been provided in humans. We aimed to assess the association of three bone-related biomarkers-25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and osteocalcin (OCN)-with several metabolic phenotypes and investigate any causal relevance to the associations using a Mendelian randomization (MR) study. Serum 25OHD, PTH, and total OCN were measured at baseline in 5169 eligible Chinese participants in Changfeng study. Partial correlation and bivariate GREML analysis were used to estimate phenotypic and genetic correlations, respectively. Multiple linear regression and logistic regression were used to assess linear associations. Genomewide association analysis (GWAS) was performed. Bidirectional two-sample MR analyses were conducted to examine causal relationships between OCN and body mass index (BMI), diastolic blood pressure (DBP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), glycated hemoglobin A1c (HbA1c), and type 2 diabetes (T2DM), using our GWAS result of OCN and GWAS statistics from Biobank Japan project (BBJ) and the largest meta-analysis of T2DM GWAS in East Asian population. Circulating OCN was significantly associated with higher DBP and HDL-C and decreased TG, blood glucose level, insulin resistance, liver fat content, bone mineral density, BMI, and a favorable body fat distribution pattern. GWAS identified one novel se...