Celiac disease and attention-deficit/hyperactivity disorder: a bidirectional Mendelian randomization analysis

Area of Science:

• Genetics
• Gastroenterology
• Neurodevelopmental Disorders

Background:

• Observational studies suggest a possible link between celiac disease (CeD) and attention-deficit/hyperactivity disorder (ADHD).
• The underlying genetic relationship between CeD and ADHD remains largely unexplored.
• Investigating genetic causality is crucial for understanding potential shared mechanisms.

Purpose of the Study:

• To assess the potential genetic causality between celiac disease and attention-deficit/hyperactivity disorder.
• To perform a bidirectional Mendelian randomization (MR) analysis to investigate the genetic relationship.
• To determine if genetic predisposition to CeD influences ADHD risk, and vice versa.

Main Methods:

• Utilized a bidirectional Mendelian randomization (MR) approach.
• Selected single nucleotide polymorphisms (SNPs) from large-scale genome-wide association studies (GWAS).
• Employed multiple MR methods (IVW, WM, MR-Egger) and performed sensitivity analyses to ensure robustness.

Main Results:

• No significant genetic association was found between celiac disease and ADHD in the primary analysis (fe-IVW: OR = 1.003, P = 0.934).
• Reverse MR analysis also showed no evidence of a genetic relationship between ADHD and CeD (fe-IVW: OR = 0.850, P = 0.378).
• Sensitivity analyses indicated no significant horizontal pleiotropy or heterogeneity, though statistical power was limited.

Conclusions:

• The study did not find compelling evidence for a genetic association between CeD and ADHD in the European population.
• Limited statistical power may have constrained the detection of causal effects.
• Future MR studies with larger sample sizes and diverse populations are recommended for further investigation.