Using polygenic scores in combination with symptom rating scales to identify attention-deficit/hyperactivity disorder

André Høberg; Berit Skretting Solberg; Tor-Arne Hegvik; Jan Haavik

doi:10.1186/s12888-024-05925-7

Using polygenic scores in combination with symptom rating scales to identify attention-deficit/hyperactivity disorder

BMC Psychiatry. 2024 Jun 27;24(1):471. doi: 10.1186/s12888-024-05925-7.

Authors

André Høberg¹, Berit Skretting Solberg^{2

3}, Tor-Arne Hegvik^{4

5}, Jan Haavik^{2

6}

Affiliations

¹ Department of Biomedicine, University of Bergen, Bergen, 5009, Norway. niz015@uib.no.
² Department of Biomedicine, University of Bergen, Bergen, 5009, Norway.
³ Child- and adolescent psychiatric outpatient unit, Hospital Betanien, Bergen, Norway.
⁴ Clinic of Surgery, St. Olavs Hospital, Trondheim, Norway.
⁵ Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
⁶ Bergen Center for Brain Plasticity, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.

Abstract

Background: The inclusion of biomarkers could improve diagnostic accuracy of attention-deficit/hyperactivity disorder (ADHD). One potential biomarker is the ADHD polygenic score (PGS), a measure of genetic liability for ADHD. This study aimed to investigate if the ADHD PGS can provide additional information alongside ADHD rating scales and examination of family history of ADHD to distinguish between ADHD cases and controls.

Methods: Polygenic scores were calculated for 576 adults with ADHD and 530 ethnically matched controls. ADHD PGS was used alongside scores from the Wender-Utah Rating Scale (WURS) and the Adult ADHD Self-Report Scale (ASRS) as predictors of ADHD diagnosis in a set of nested logistic regression models. These models were compared by likelihood ratio (LR) tests, Akaike information criterion corrected for small samples (AICc), and Lee R². These analyses were repeated with family history of ADHD as a covariate in all models.

Results: The ADHD PGS increased the variance explained of the ASRS by 0.58% points (pp) (R²_ASRS = 61.11%, R²_{ASRS + PGS}=61.69%), the WURS by 0.61pp (R²_WURS = 77.33%, R²_{WURS + PGS}= 77.94%), of ASRS and WURS together by 0.57pp (R²_{ASRS + WURS}=80.84%, R²_{ASRS + WURS+PGS}=81.40%), and of self-reported family history by 1.40pp (R²_family = 28.06%, R²_{family + PGS}=29.46%). These increases were statistically significant, as measured by LR tests and AICc.

Conclusion: We found that the ADHD PGS contributed additional information to common diagnostic aids. However, the increase in variance explained was small, suggesting that the ADHD PGS is currently not a clinically useful diagnostic aid. Future studies should examine the utility of ADHD PGS in ADHD prediction alongside non-genetic risk factors, and the diagnostic utility of the ADHD PGS should be evaluated as more genetic data is accumulated and computational tools are further refined.

Keywords: Attention deficit hyperactivity disorder; Diagnosis; Genetics; Polygenic risk score; Polygenic score; Prediction.

MeSH terms

Adult
Attention Deficit Disorder with Hyperactivity* / diagnosis
Attention Deficit Disorder with Hyperactivity* / genetics
Case-Control Studies
Female
Genetic Predisposition to Disease / genetics
Humans
Male
Middle Aged
Multifactorial Inheritance* / genetics
Psychiatric Status Rating Scales*
Self Report