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Genetically determined type 1 diabetes mellitus and risk of osteoporosis

骨质疏松症 医学 置信区间 孟德尔随机化 股骨颈 骨矿物 优势比 内科学 遗传学 生物 遗传变异 基因型 基因
作者
Ting Cheng,Jia-Lin Hou,Ziyi Han,Xin-Lei Geng,Yaochen Zhang,Keyi Fan,Liu Liu,Heyi Zhang,Yue-Hong Huo,Xiaofeng Li,Sheng‐Xiao Zhang
出处
期刊:Experimental Gerontology [Elsevier]
卷期号:191: 112434-112434 被引量:1
标识
DOI:10.1016/j.exger.2024.112434
摘要

Observational evidence suggests that type 1 diabetes mellitus (T1DM) is associated with the risk of osteoporosis (OP). Nevertheless, it is not apparent whether these correlations indicate a causal relationship. To elucidate the causal relationship, a two-sample Mendelian randomization (MR) analysis was performed. T1DM data was obtained from the large genome-wide association study (GWAS), in which 6683 cases and 12,173 controls from 12 European cohorts were involved. Bone mineral density (BMD) samples at four sites were extracted from the GEnetic Factors for OSteoporosis (GEFOS) consortium, including forearm (FA) (n = 8,143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). The former three samples were from mixed populations and the last one was from European. Inverse variance weighting, MR-Egger, and weighted median tests were used to test the causal relationship between T1DM and OP. A series of sensitivity analyses were then conducted to verify the robustness of the results. Twenty-three independent SNPs were associated with FN-BMD and LS-BMD, twenty-seven were associated with FA-BMD, and thirty-one were associated with eBMD. Inverse variance-weighted estimates indicated a causal effect of T1DM on FN-BMD (odds ratio (OR) =1.033, 95 % confidence interval (CI): 1.012–1.054, p = 0.002) and LS-BMD (OR = 1.032, 95 % CI: 1.005–1.060, p = 0.022) on OP risk. Other MR methods, including weighted median and MR-Egger, calculated consistent trends. While no significant causation was found between T1DM and the other sites (FA-BMD: OR = 1.008, 95 % CI: 0.975–1.043, p = 0.632; eBMD: OR = 0.993, 95 % CI: 0.985–1.001, p = 0.106). No significant heterogeneity (except for eBMD) or horizontal pleiotropy was found for instrumental variables, suggesting these results were reliable and robust. This study shows a causal relationship between T1DM and the risk of some sites of OP (FN-BMD, LS-BMD), allowing for continued research to discover the clinical and experimental mechanisms of T1DM and OP. It also contributes to the recommendation if patients with T1DM need targeted care to promote bone health and timely prevention of osteoporosis.
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