Impact of ADHD Polygenic Score on Diagnostic Aids and Variance Explained in ADHD Assessment

The following is a summary of “Using polygenic scores in combination with symptom rating scales to identify attention-deficit/hyperactivity disorder,” published in the June 2024 issue of Psychiatry by Høberg et al.

Current attention-deficit/hyperactivity disorder (ADHD) diagnosis lacks precision, and incorporating genetic susceptibility through ADHD polygenic scores (PGS) could enhance its accuracy.

Researchers conducted a retrospective study exploring whether ADHD-PGS improves differentiation between ADHD and controls, compared to symptom scales and family history.

They computed PGS for 576 adults diagnosed with ADHD and 530 controls matched ethnically. Logistic regression models were constructed using ADHD-PGs, along with scores from the Wender-Utah Rating Scale (WURS) and the Adult ADHD Self-Report Scale (ASRS), to predict ADHD diagnosis. Model comparisons were conducted using likelihood ratio (LR) tests, Akaike information criterion corrected for small samples (AICc), and Lee R². The analyses were repeated while including a family history of ADHD as a covariate in all models.

The result showed that ADHD-PGS contributed to an increase in the explained variance of the ASRS by 0.58 percentage points (pp) (R^2_ASRS = 61.11%, R^{2_{ASRS + PGS}}=61.69%), of the WURS by 0.61 pp (R^{2 _WURS} = 77.33%, R^{2_{WURS + PGS}}= 77.94%), of both ASRS and WURS together by 0.57 pp (R^{2_{ASRS + WURS}}=80.84%, R^{2_{ASRS + WURS+PGS}}=81.40%), and of self-reported family history by 1.40 pp (R^2_family = 28.06%, R^{2_{family + PGS}}=29.46%). The increases were statistically significant based on likelihood ratio tests and AICc.

Investigators concluded that ADHD-PGS enhances diagnostic information but showed limited clinical utility due to the small variance explained, necessitating further research integrating non-genetic risk factors and evaluating its diagnostic potential as genetic data accumulates and computational tools are further refined.

Source: bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-024-05925-7

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