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

[ Vol. 19 , Issue. 4 ]

Author(s):

He Zhuang, Ying Zhang, Shuo Yang, Liang Cheng* and Shu-Lin Liu*   Pages 224 - 231 ( 8 )

Abstract:


Objective: 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.

Materials and Methods: 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.

Results: 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.

Conclusion: 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.

Keywords:

Infant length, T2DM, mendelian randomization, causal effect, instrumental variables, MR-egger.

Affiliation:

Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China), Harbin Medical University, Harbin, Department of Pharmacy, Heilongjiang Province Land Reclamation Headquarters General Hospital, 150001, Harbin, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China), Harbin Medical University, Harbin

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