2 型糖尿病对骨质疏松症有保护作用——孟德尔随机化分析。

Type 2 diabetes mellitus plays a protective role against osteoporosis --mendelian randomization analysis.

机构信息

Graduate School, Wuhan Sports University, Wuhan, 430079, Hubei, China.

College of Acupuncture-Moxibustion and Tuina, Anhui University of Chinese Medicine, Hefei, 230012, Anhui, China.

出版信息

BMC Musculoskelet Disord. 2023 Jun 2;24(1):444. doi: 10.1186/s12891-023-06528-1.

Abstract

BACKGROUND

Type 2 diabetes mellitus (DM2) and osteoporosis (OP) are currently the two most significant causes of mortality and morbidity in older adults, according to clinical evidence. The intrinsic link between them is yet unknown, despite reports of their coexistence. By utilizing the two-sample Mendelian randomization (MR) approach, we sought to evaluate the causal impact of DM2 on OP.

METHODS

The aggregate data of the whole gene-wide association study (GWAS) were analyzed. A two-sample MR analysis was performed using single-nucleotide polymorphisms (SNPs), which are strongly associated with DM2, as instrumental variables (IVs) to evaluate the causal analysis of DM2 on OP risk with OR values, using inverse variance weighting, MR-egger regression, and weighted median methods, respectively.

RESULT

A total of 38 single nucleotide polymorphisms were included as tool variables. According to the results of inverse variance-weighted (IVW), we found that there was a causal relationship between DM2 and OP, in which DM2 had a protective effect on OP. For each additional case of DM2, there is a 0.15% decrease in the odds of developing OP (OR = 0.9985;95%confidence interval:0.9974,0.9995; P value = 0.0056). There was no evidence that the observed causal effect between DM2 and the risk of OP was affected by genetic pleiotropy (P = 0.299). Using Cochran Q statistics and MR-Egger regression in the IVW approach, the heterogeneity was calculated; P > 0.05 shows that there is a significant amount of heterogeneity.

CONCLUSION

A causal link between DM2 and OP was established by MR analysis, which also revealed that DM2 decreased the occurrence of OP.

摘要

背景

根据临床证据,2 型糖尿病(DM2)和骨质疏松症(OP)是目前导致老年人死亡率和发病率最高的两个主要原因。尽管有报告称两者同时存在,但它们之间的内在联系尚不清楚。我们利用两样本孟德尔随机化(MR)方法,评估了 DM2 对 OP 的因果影响。

方法

分析了全基因范围关联研究(GWAS)的汇总数据。使用与 DM2 密切相关的单核苷酸多态性(SNP)作为工具变量(IV)进行两样本 MR 分析,分别采用逆方差加权、MR-egger 回归和加权中位数方法,以 OR 值评估 DM2 对 OP 风险的因果分析。

结果

共纳入 38 个单核苷酸多态性作为工具变量。根据逆方差加权(IVW)的结果,我们发现 DM2 与 OP 之间存在因果关系,其中 DM2 对 OP 具有保护作用。每增加一例 DM2,OP 的发病几率降低 0.15%(OR=0.9985;95%置信区间:0.9974,0.9995;P 值=0.0056)。没有证据表明观察到的 DM2 与 OP 风险之间的因果效应受到遗传多效性的影响(P=0.299)。在 IVW 方法中,使用 Cochran Q 统计量和 MR-Egger 回归计算异质性;P>0.05 表示存在大量异质性。

结论

MR 分析确立了 DM2 与 OP 之间的因果关系,也表明 DM2 降低了 OP 的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbc6/10236750/3b487969439f/12891_2023_6528_Fig1_HTML.jpg

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