New insights on polygenic risk in ADHD

Attention-deficit/hyperactivity disorder (ADHD) is highly heritable, yet its genetic architecture is complex. Twin studies estimate heritability at approximately 76%, while current genome-wide association studies (GWAS), identifying 39 independent loci, explain 11–22% of SNP-based heritability. Importantly, ADHD shares genetic liability with multiple psychiatric disorders, challenging categorical models of psychopathology and providing a genetic framework for its frequent psychiatric comorbidity.

This talk will examine how polygenic scores (PGS) are reshaping our understanding of ADHD. By aggregating the effects of thousands of common variants, ADHD PGS show dose-dependent associations with diagnosis and symptom burden across the population. Polygenic risk is highest among individuals with persistent ADHD and differs across developmental trajectories, including childhood-onset and later-diagnosed ADHD. Genetic liability also extends beyond core ADHD symptoms, linking ADHD PGS to emotional and behavioural problems, cognitive and educational outcomes, and a broad range of medical traits.

Sex-specific analyses provide further insight: females with ADHD do not appear to carry a greater common-variant genetic burden than males, but ADHD genetic liability may be more likely to manifest as, or be clinically diagnosed as, anxiety or depression in females.

Together, these findings position PGS as powerful tools for moving beyond diagnostic categories towards a developmental and dimensional understanding of ADHD, illuminating its lifecourse, genetic overlap and gene–environment interplay. Although not yet ready for clinical use, PGS may ultimately contribute to earlier identification, risk stratification and treatment optimisation.