Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, China.
Osteoporos Int. 2023 Jun;34(6):1111-1117. doi: 10.1007/s00198-023-06734-6. Epub 2023 Apr 3.
We used two-sample Mendelian Randomization to reveal causal estimates of type 1 diabetes and bone. Type 1 diabetes was found to be a risk factor for bone metabolic health, although there was no clear evidence to support a genetic association between type 1 diabetes and osteoporosis and fracture risk.
Based on the random assignment of gametes at conception, Mendelian randomization (MR) analysis simulates randomized controlled trials in an observational setting. Therefore, we used MR to assess the association causality of type 1 diabetes (T1D) with fractures and osteoporosis.
From a genome-wide association meta-analysis, independent single nucleotide polymorphisms closely associated with T1D were selected as instrumental variables. Data on fracture and osteoporosis were obtained from the FinnGen Consortium. We performed a two-sample MR analysis, using inverse-variance weighted (IVW) as the primary analysis method, to assess possible causal associations between T1D and bone risk. The results were verified by MR-Egger regression and median weighted method (WME). MR-PRESSO and MR-Egger intercepts were used to evaluate the horizontal pleiotropy of instrumental variables, and the Q-test and "leave-one-out" methods were used to test the heterogeneity of MR results.
IVW (OR=1.040, 95% CI=0.974-1.109, P=0.238), MR-Egger regression (OR=1.077, 95% CI=0.921-1.260, P=0.372) and WME (OR=1.021, 95% CI=0.935-1.114, P=0.643) all showed that there was no causal relationship between T1D and osteoporosis, but the direction was consistent. The indicative significance of IVW results in T1D and forearm fractures (OR=1.062, 95% CI=1.010-1.117, P=0.020), but the results are not robust enough. There was no causal effect in femur, lumbar and pelvis, or shoulder and upper arm fractures.
After MR analysis, although T1D may be a risk factor for bone health, we do not have sufficient evidence to support a causal effect of T1D on osteoporosis and fractures at a genetically predicted level. More cases need to be included for analysis.
我们使用两样本孟德尔随机化来揭示 1 型糖尿病和骨骼的因果关系。虽然没有明确的证据支持 1 型糖尿病与骨质疏松症和骨折风险之间存在遗传关联，但 1 型糖尿病被发现是骨骼代谢健康的危险因素。
从全基因组关联荟萃分析中，选择与 1 型糖尿病密切相关的独立单核苷酸多态性作为工具变量。骨折和骨质疏松症的数据来自芬兰人基因联盟。我们进行了两样本孟德尔随机分析，使用逆方差加权（IVW）作为主要分析方法，评估 1 型糖尿病与骨骼风险之间可能的因果关系。使用 MR-Egger 回归和中位数加权法（WME）验证结果。MR-PRESSO 和 MR-Egger 截距用于评估工具变量的水平多效性，Q 检验和“逐个剔除”方法用于检验 MR 结果的异质性。
IVW（OR=1.040，95%CI=0.974-1.109，P=0.238）、MR-Egger 回归（OR=1.077，95%CI=0.921-1.260，P=0.372）和 WME（OR=1.021，95%CI=0.935-1.114，P=0.643）均表明 1 型糖尿病与骨质疏松症之间没有因果关系，但方向一致。IVW 结果在 1 型糖尿病和前臂骨折（OR=1.062，95%CI=1.010-1.117，P=0.020）中具有指示意义，但结果不够稳健。在股骨、腰椎和骨盆、肩部和上臂骨折中没有因果效应。
经过 MR 分析，虽然 1 型糖尿病可能是骨骼健康的危险因素，但我们没有足够的证据支持在遗传预测水平上 1 型糖尿病对骨质疏松症和骨折的因果效应。需要纳入更多病例进行分析。
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