Research Paper Volume 13, Issue 2 pp 2015—2030
Mendelian randomization study of telomere length and bone mineral density
- 1 Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- 2 Department of Otorhinolaryngology, The Third Hospital of Wuhan, Wuhan 430070, China
- 3 School of Computer Science, Northwestern Polytechnical University, Xi’an 710072, China
Received: July 16, 2020 Accepted: October 22, 2020 Published: December 15, 2020https://doi.org/10.18632/aging.202197
How to Cite
Copyright: © 2020 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Purpose: Some epidemiological studies and animal studies have reported a relationship between leukocyte telomere length (LTL) and bone mineral density (BMD). However, the causality underlying the purported relationship has not been determined. Here we performed a two-sample MR analysis to test the causal link between telomere length and BMD.
Results: Our research suggested no causal link of LTL and BMD using IVW method. The weighted median, MR-Egger regression and MR.RAPS method yielded a similar pattern of effects. MR-Egger intercept test demonstrated our results were not influenced by pleiotropy. Heterogeneities among the genetic variants on heel estimated BMD and TB-BMD vanished after excluding rs6028466. “Leave-one-out” sensitivity analysis confirmed the stability of our results.
Conclusion: Our MR analysis did not support causal effect of telomere length on BMD.
Methods: We utilized 5 independent SNPs robustly associated with LTL as instrument variables. The outcome results were obtained from GWAS summary data of BMD. The two-sample MR analysis was conducted using IVW, weighted median, MR-Egger regression and MR.RAPS method. MR-Egger intercept test, Cochran’s Q test and I2 statistics and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities and stability of these genetic variants on BMD.
BMD: bone mineral density; DXA: dual-energy X-ray absorptiometry; BMI: body mass index; LTL: leukocyte telomere length; RCT: randomized controlled trial; MR: Mendelian randomization; IV: instrument variable; GWAS: genome-wide association study; SNP: single-nucleotide polymorphism; LD: linkage disequilibrium; FN-BMD: Femoral Neck bone mineral density; LS-BMD: Lumbar Spine bone mineral density; FA-BMD: Forearm bone mineral density; TB-BMD: Total Body-bone mineral density; IVW: inverse variance weighting; WM: weighted median; MR.RAPS: Robust Adjusted Profile Score; GEFOS: GEnetic Factors for OSteoporosis Consortium.