Detecting causal relationship between metabolic traits and osteoporosis using multivariable Mendelian randomization
- PDF / 816,319 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 86 Downloads / 191 Views
ORIGINAL ARTICLE
Detecting causal relationship between metabolic traits and osteoporosis using multivariable Mendelian randomization Q. Zhang 1,2 & J. Greenbaum 2 & H. Shen 2 & L.-J. Zhao 2 & W.-D. Zhang 3 & C.-Q. Sun 1,3 & H.-W. Deng 2 Received: 10 February 2020 / Accepted: 15 September 2020 # International Osteoporosis Foundation and National Osteoporosis Foundation 2020
Abstract Summary By adopting the extension approaches of Mendelian randomization, we successfully detected and prioritized the potential causal risk factors for BMD traits, which might provide us novel insights for treatment and intervention into bonerelated complex traits and diseases. Introduction Osteoporosis (OP) is a common metabolic skeletal disease characterized by reduced bone mineral density (BMD). The identified SNPs for BMD can only explain approximately 10% of the variability, and very few causal factors have been identified so far. Methods The Mendelian randomization (MR) approach enables us to assess the potential causal effect of a risk factor on the outcome by using genetic IVs. By using extension methods of MR—multivariable MR (mvMR) and MR based on Bayesian model averaging (MR-BMA)—we intend to estimate the causal relationship between fifteen metabolic risk factors for BMD and try to prioritize the most potential causal risk factors for BMD. Results Our analysis identified three risk factors T2D, FG, and HCadjBMI for FN BMD; four risk factors FI, T2D, HCadjBMI, and WCadjBMI for FA BMD; and three risk factors FI, T2D, and HDL cholesterol for LS BMD, and all risk factors were causally associated with heel BMD except for triglycerides and WCadjBMI. Consistent with the mvMR results, MR-BMA confirmed those risk factors as top risk factors for each BMD trait individually. Conclusions By combining MR approaches, we identified the potential causal risk factors for FN, FA, LS, and heel BMD individually and we also prioritized and ranked the potential causal risk factors for BMD, which might provide us novel insights for treatment and intervention into bone-related complex traits and diseases. Keywords Causal relationship . Mendelian randomization . Multivariable MR . Osteoporosis
Introduction Osteoporosis (OP), a common metabolic skeletal disease, is mainly characterized by reduced bone mineral density (BMD) that results in increased risk for bone fragility and eventually
bone fractures. BMD, a highly heritable trait and an important index of bone strength, is frequently used in for OP clinical diagnosis and genetic research. Previous studies estimated that nearly 75% of the variance in BMD at the site of the femoral neck (FN) and 83% in the lumbar spine (LS) may be explained
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00198-020-05640-5) contains supplementary material, which is available to authorized users. * H.-W. Deng [email protected] 1
School of Nursing and Health, Zhengzhou University, NO.101 Kexue Road, High-Tech Development Zone of States, Zhengzhou 450001, People’s Republ
Data Loading...
