Psychiatric Polygenic Risk Scores as Predictor for Attention Deficit/Hyperactivity Disorder and Autism Spectrum...

Area of Science:

• Neurogenetics
• Psychiatric disorders
• Genomic epidemiology

Background:

• Attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental disorders.
• Single nucleotide polymorphisms (SNPs) contribute to genetic risk, enabling polygenic risk score (PRS) calculations.

Purpose of the Study:

• To investigate the association between PRS for ADHD, ASD, and schizophrenia (SCZ) and diagnoses of ADHD and ASD in a clinical child and adolescent population.
• To determine if PRS for one disorder predicts diagnoses in related neurodevelopmental conditions.

Main Methods:

• Calculated PRS for ADHD, ASD, and SCZ using genome-wide association study data.
• Analyzed associations using logistic regression in a clinical sample (N=688) and adult controls (N=943).
• Tested associations with single ADHD diagnosis (N=280), single ASD diagnosis (N=295), and combined ADHD/ASD diagnoses (N=688).

Main Results:

• ADHD PRS showed a significant association with ADHD diagnosis (OR 1.6, P=1.39×10⁻⁷).
• ADHD PRS was also significantly associated with the combined ADHD/ASD diagnosis group (OR 1.36, P=1.21×10⁻⁵).
• No significant associations were found for ASD PRS, SCZ PRS, or ADHD PRS with isolated ASD diagnosis.

Conclusions:

• The PRS for ADHD is significantly associated with ADHD status and the combined ADHD/ASD diagnosis group.
• The association with the combined group is mainly driven by ADHD status, suggesting disorder-specific genetic influences of the ADHD PRS.
• These findings highlight the genetic overlap and specificity between ADHD and ASD.