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Support for association between ADHD and two candidate genes: NET1 and DRD1
Aaron J Bobb1, Anjene M Addington, Ellen Sidransky
1Child Psychiatry Branch, NIMH, NIH, Bethesda, Maryland 20892-1600, USA.
Summary
This study found significant genetic links between attention deficit hyperactivity disorder (ADHD) and specific gene variations in NET1 and DRD1. These findings highlight potential genetic markers for ADHD, though no direct impact on behavior or brain structure was observed.
Area of Science:
- Neurogenetics
- Psychiatric Genetics
- Human Genetics
Background:
- Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a substantial genetic component.
- Candidate genes, including norepinephrine transporter (NET1) and dopamine D1 receptor (DRD1), are frequently investigated for their role in ADHD etiology.
- Previous research implicated NET1 due to treatment responses and DRD1 through animal models.
Purpose of the Study:
- To investigate the association between ADHD and polymorphisms in 12 candidate genes.
- To explore the relationship between genetic variations and behavioral, cognitive, and neuroanatomical measures in ADHD.
- To compare findings from case-control and family-based genetic analyses.
Main Methods:
- DNA analysis of 163 ADHD probands, 192 parents, and 129 healthy controls.
- Investigated polymorphisms in 12 candidate genes using case-control and family-based (Transmission Disequilibrium Test - TDT) methods.
- Correlated genetic findings with dimensional measures of behavior, cognition, and brain MRI volumes.
Main Results:
- Significant association found between two NET1 single nucleotide polymorphisms (SNPs) and ADHD via TDT (P ≤ 0.009).
- Significant association identified between two DRD1 SNPs and ADHD using case-control analysis (P ≤ 0.008).
- No significant differences in behavioral, cognitive, or brain MRI volumes were observed across NET1 or DRD1 genotypes.
Conclusions:
- This study supports an association between ADHD and polymorphisms in both the NET1 and DRD1 genes.
- Genetic variations in ten other candidate genes examined were not significantly associated with ADHD in this cohort.
- The divergent results between family-based and case-control methods emphasize the importance of employing both approaches in ADHD genetic research.