A Mendelian Randomization Study of Infant Length and Type 2 Diabetes Mellitus Risk.

OBJECTIVE Infant length (IL) is a positive associated phenotype of type 2 diabetes mellitus (T2DM), but the casual relationship of which is still blur. Here, we applied a Mendelian randomization (MR) study to explore the casual relationship between IL and T2DM, which has the potential to provide guidance for assessing T2DM activity and T2DM- prevention in young at-risk populations. MATERIALS AND METHODS To classify it, a Two-sample MR, using genetic instrumental variables (IVs) to explore the casual effect, was utilized here 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 inverse-variance weighted method for the assessment the risk the shorter IL brings to T2DM. The sensitivity validation was conducted to identify the effect of individual SNPs. MR-Egger regression was used to detect pleiotropic bias of IVs. RESULTS The pooled odds ratio from the IVW method was 1.03 (95% CI 0.89 -1.18, P = 0.0785), low intercept (-0.477, P = 0.252), and small fluctuation of ORs (from -0.062 ((0.966 - 1.03) / 1.03) to 0.05 ((1.081 - 1.03) / 1.03)) in leave-one-out validation. CONCLUSIONS We validated that the shorter IL contributes no additional risk to T2DM. The sensitivity analysis and the MR-Egger regression analysis also provided adequate evidence the above result was not due to any heterogeneity or pleiotropic effect of IVs.