Risk cycling in diabetes and autism spectrum disorder: a bidirectional Mendelian randomization study

Area of Science:

• Genetics
• Epidemiology
• Public Health

Background:

• The relationship between diabetes mellitus (DM) and autism spectrum disorder (ASD) is debated.
• Understanding potential causal links is crucial for public health interventions.

Purpose of the Study:

• To investigate the bidirectional causal relationship between different types of DM (T1DM, T2DM, GDM) and ASD using Mendelian randomization (MR).

Main Methods:

• Utilized genome-wide association study data for single nucleotide polymorphisms related to T1DM, T2DM, GDM, and ASD.
• Employed inverse variance weighted, MR-Egger, and weighted median methods for causality analysis.
• Assessed pleiotropy, heterogeneity, and result sensitivity using MR-Egger intercept, Cochran's Q, and leave-one-out analyses.

Main Results:

• Type 2 diabetes mellitus (T2DM) showed a bidirectional causal association with an increased risk of autism spectrum disorder (ASD).
• No significant causal relationship was found between type 1 diabetes mellitus (T1DM) or gestational diabetes mellitus (GDM) and ASD.
• Sensitivity analyses confirmed the robustness of the findings, with no significant horizontal pleiotropy or heterogeneity.

Conclusions:

• T2DM and ASD are identified as reciprocal risk factors, potentially contributing to an intergenerational risk cycle, particularly in females.
• Aggressive prevention and treatment strategies for T2DM and ASD are recommended to disrupt this cycle.
• The study does not support a causal link between T1DM or GDM and ASD, highlighting the need for further research into underlying mechanisms.