Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China), Harbin Medical University, Harbin, China.
HMU-UCFM Centre for Infection and Genomics, Harbin Medical University, Harbin, China.
Curr Gene Ther. 2019;19(4):224-231. doi: 10.2174/1566523219666190925115535.
Infant length (IL) is a positively associated phenotype of type 2 diabetes mellitus (T2DM), but the causal relationship of which is still unclear. Here, we applied a Mendelian randomization (MR) study to explore the causal relationship between IL and T2DM, which has the potential to provide guidance for assessing T2DM activity and T2DM- prevention in young at-risk populations.
To classify the study, a two-sample MR, using genetic instrumental variables (IVs) to explore the causal effect was applied to test the influence of IL on the risk of T2DM. In this study, MR was carried out on GWAS data using 8 independent IL SNPs as IVs. The pooled odds ratio (OR) of these SNPs was calculated by the inverse-variance weighted method for the assessment of the risk the shorter IL brings to T2DM. Sensitivity validation was conducted to identify the effect of individual SNPs. MR-Egger regression was used to detect pleiotropic bias of IVs.
The pooled odds ratio from the IVW method was 1.03 (95% CI 0.89-1.18, P = 0.0785), low intercept was -0.477, P = 0.252, and small fluctuation of ORs ranged from -0.062 ((0.966 - 1.03) / 1.03) to 0.05 ((1.081 - 1.03) / 1.03) in leave-one-out validation.
We validated that the shorter IL causes no additional risk to T2DM. The sensitivity analysis and the MR-Egger regression analysis also provided adequate evidence that the above result was not due to any heterogeneity or pleiotropic effect of IVs.
婴儿身长（IL）与 2 型糖尿病（T2DM）呈正相关表型，但因果关系尚不清楚。在这里，我们应用孟德尔随机化（MR）研究来探讨 IL 与 T2DM 之间的因果关系，这可能为评估年轻高危人群的 T2DM 活动和 T2DM 预防提供指导。
为了进行分类研究，应用两样本 MR 方法，使用遗传工具变量（IVs）来探索 IL 对 T2DM 风险的因果影响。本研究使用 8 个独立的 IL SNP 作为 IVs ，对 GWAS 数据进行 MR 分析。采用逆方差加权法计算这些 SNP 的合并优势比（OR），以评估较短的 IL 对 T2DM 的风险。进行敏感性验证以识别个体 SNP 的影响。采用 MR-Egger 回归检测 IVs 的偏倚。
IVW 方法的合并 OR 为 1.03（95%CI 0.89-1.18，P=0.0785），低截距为-0.477，P=0.252，OR 波动范围较小，从-0.062（（0.966-1.03）/1.03）到 0.05（（1.081-1.03）/1.03）。在逐一剔除验证中。
我们验证了较短的 IL 不会导致 T2DM 的额外风险。敏感性分析和 MR-Egger 回归分析也提供了充分的证据，表明上述结果不是由于 IVs 的任何异质性或偏倚效应所致。
