The FMR1 premutation and attention-deficit hyperactivity disorder (ADHD): evidence for a complex inheritance

Area of Science:

• Neurogenetics
• Behavioral Genetics

Background:

• Attention-deficit hyperactivity disorder (ADHD) symptoms are observed in adult female carriers of the FMR1 premutation.
• The role of polygenic inheritance in ADHD among FMR1 premutation carriers requires further investigation.

Purpose of the Study:

• To investigate the contribution of polygenes to ADHD symptoms in females carrying the FMR1 premutation.
• To determine the proportion of variance in ADHD symptoms attributable to residual genetic factors after accounting for the FMR1 premutation's effect.

Main Methods:

• Familial aggregation analysis was conducted on 231 females from 82 pedigrees.
• Connors Adult ADHD Rating Scales were used to assess ADHD symptoms.

Main Results:

• Significant residual polygenic effects were found for ADHD Index scores (p=0.0117) and self-concept problems (p=0.0110).
• The FMR1 premutation explained approximately 5% of the variance in these ADHD symptoms.
• Polygenes accounted for about 50% of the residual variance, indicating a substantial genetic contribution beyond FMR1.

Conclusions:

• ADHD symptoms in FMR1 premutation carriers are influenced by both the FMR1 premutation and additional polygenic factors.
• These findings suggest a complex genetic architecture for ADHD, involving interactions between specific gene mutations and multiple genetic loci.