Causal relationship between type 2 diabetes mellitus and bone mineral density: a Mendelian randomization study in an East Asian population

• Published in: Osteoporosis international Vol. 34; no. 10; pp. 1719 - 1727
• Main Authors: Huang, Guiwu, Chen, Xiong, Chen, Yanbo, Liu, Wenzhou, Chen, Chen, Song, Weidong, Zeng, Gang
• Format: Journal Article
• Language: English
• Published: London Springer London 01.10.2023; Springer Nature B.V
• Subjects: Asian people; Bone density; Bone mineral density; Cognition; Diabetes; Diabetes mellitus (non-insulin dependent); Endocrinology; Gene polymorphism; Genetic diversity; Genome-wide association studies; Genomes; Medicine; Medicine & Public Health; Original; Original Article; Orthopedics; Osteoporosis; Pleiotropy; Population studies; Rheumatology; Sensitivity analysis; Osteoporosis; Bone mineral density; Mendelian randomization; Type 2 diabetes mellitus
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-023-06807-6

Summary It remains unclear whether the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) reflects causality in East Asian populations. Herein, a Mendelian randomization study conducted in East Asian population enhances the current clinical cognition that T2DM is not associated with reduction in BMD. Purpose A Mendelian randomization (MR) approach was utilized to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in East Asian populations. Methods Genome-wide association study summary data from BioBank Japan were used to identify genetic variants strongly related to T2DM risk (36,614 cases and 155,150 controls) and osteoporosis (7788 cases and 204,665 controls). Heel BMD GWAS data of 1260 East Asian people from ieu open gwas project was considered as a second outcome. Inverse variance-weighted (IVW) analysis was mainly applied; MR-Egger and the weighted median were also used to obtain robust estimates. A series of sensitivity analyses including Cochran’s Q test, MR-Egger regression, and leave-one-out analysis were used to detect pleiotropy or heterogeneity. Results In the main analysis, IVW estimates indicated that T2DM significantly associated with the risk of osteoporosis (odds ratio = 0.92, 95% CI: 0.86–0.99, p  = 0.016) and with higher BMD (OR: 1.25, 95% CI: 1.06–1.46, p  = 6.49 × 10 −3 ). Results of comprehensive sensitivity analysis were consistent with the main causality estimate. Horizontal pleiotropy and heterogeneity were absent in our MR study. Conclusions T2DM is not associated with reduction in BMD in terms of genetic polymorphism in East Asian populations.