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Genetic Causal Relationship Between Alanine Aminotransferase Levels and Risk of Gestational Diabetes Mellitus: Mendelian Randomization Analysis Based on Two Samples

Published online by Cambridge University Press:  18 April 2024

Lihua Yin ,
Yifang Hu ,
Xiaoxia Hu ,
Xiaolei Huang ,
Yingyuan Chen  and
Yisheng Zhang Open the ORCID record for Yisheng Zhang [Opens in a new window]
Lihua Yin
Affiliation:
The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
Yifang Hu
Affiliation:
The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
Xiaoxia Hu
Affiliation:
The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
Xiaolei Huang
Affiliation:
The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
Yingyuan Chen
Affiliation:
The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
Yisheng Zhang*
Affiliation:
The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China
*
Corresponding author: Yisheng Zhang; Email: zhangysnbu@163.com
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Abstract

Gestational diabetes mellitus (GDM) is a frequent complication of pregnancy. The specific mechanisms underlying GDM have not yet been fully elucidated. Contemporary research indicates a potential association between liver enzyme irregularities and an increased risk of metabolic disorders, including diabetes. The alanine aminotransferase (ALT) level is recognized as a sensitive marker of liver injury. An increase in ALT levels is hypothesized to be linked to the pathogenesis of insulin resistance and diabetes. Nonetheless, the definitive causal link between ALT levels and GDM still needs to be determined. This investigation utilized two-sample Mendelian randomization (MR) to examine the genetic causation between alanine aminotransferase (ALT) and GDM. We acquired alanine aminotransferase (ALT)-related GWAS summary data from the UK Biobank, Million Veteran Program, Rotterdam Study, and Lifeline Study. Gestational diabetes data were obtained from the FinnGen Consortium. We employed various MR analysis techniques, including inverse-variance weighted (IVW), MR Egger, weighted median, simple, and weighted weighting. In addition to MR-Egger intercepts, Cochrane’s Q test was also used to assess heterogeneity in the MR data, and the MR-PRESSO test was used to assess horizontal pleiotropy. To assess the association’s sensitivity, a leave-one-out approach was employed. The IVW results confirmed the independent risk factor for GDM development, as indicated by the ALT level (p = .011). As shown by leave-one-out analysis, horizontal pleiotrophy did not significantly skew the causative link (p > .05). Our dual-sample MR analysis provides substantiated evidence of a genetic causal relationship between alanine aminotransferase (ALT) levels and gestational diabetes.

Keywords

Gestational diabetes mellitusferroptosis
Type
Article
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Twin Research and Human Genetics , First View , pp. 1 - 5
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Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of International Society for Twin Studies

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