GAD1 gene polymorphisms are associated with hyperactivity in Attention-Deficit/Hyperactivity Disorder

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Attention-Deficit/Hyperactivity Disorder (ADHD) is a common childhood neurodevelopmental disorder.
• γ-aminobutyric acid (GABA) signaling is implicated in ADHD, particularly hyperactive/impulsive symptoms.
• The glutamic acid decarboxylase (GAD1) gene is crucial for GABA synthesis.

Purpose of the Study:

• To investigate the association between GAD1 gene single nucleotide polymorphisms (SNPs) and ADHD susceptibility.
• To examine the influence of specific GAD1 SNPs (rs3749034 and rs11542313) on ADHD risk and symptom severity.
• To explore the role of GAD1 haplotypes in ADHD hyperactive/impulsive symptoms.

Main Methods:

• A family-based association study involving 547 families with ADHD probands.
• Evaluation of hyperactive/impulsive symptoms using parent-reported Swanson, Nolan, and Pelham Scale-version IV (SNAP-IV).
• Analysis of GAD1 SNPs rs3749034 and rs11542313, and GAD1 haplotypes for transmission disequilibrium and association with symptom scores.

Main Results:

• The C allele of GAD1 SNP rs11542313 was significantly overtransmitted to ADHD probands.
• Higher hyperactive/impulsive scores were observed in carriers of the G allele for rs3749034 and the C allele for rs11542313.
• GAD1 haplotypes, particularly the GC haplotype, were associated with elevated hyperactive/impulsive symptom scores in ADHD youths.

Conclusions:

• The GAD1 gene plays a significant role in ADHD susceptibility.
• Genetic variations within GAD1 contribute to the hyperactive/impulsive symptom domain of ADHD.
• These findings highlight GAD1 as a potential genetic marker for ADHD, especially its hyperactive/impulsive features.