This Danish population-based case-cohort study (iPSYCH2015) examined whether the genetic risk profiles of individuals diagnosed with ASD or ADHD changed over the period 1994–2016, using polygenic scores across psychiatric and cognitive-behavioral traits in 17,071 ASD and 20,111 ADHD incident cases.
More recent diagnoses were associated with lower polygenic scores for the respective disorder: ADHD genetic risk fell by –0.06 SDs per 10-year increase in diagnosis year (95% CI, –0.09 to –0.03; P=.001), and ASD genetic risk fell by –0.07 SDs per 10-year increase (95% CI, –0.10 to –0.04; P<.001). Cross-disorder polygenic scores (bipolar, schizophrenia, ASD for ADHD cases, and vice versa) also declined over time. Simulation comparisons supported broadening diagnostic criteria—not new environmental risk factors—as the primary driver of rising rates.
Full text is under embargo; analysis is limited to Denmark, which may reduce generalizability to healthcare systems with different diagnostic trajectories. The study relies on polygenic scores derived from external GWAS, which capture only common genetic variation and may not reflect rare variant contributions. Secular changes in ascertainment and healthcare access could confound year-of-diagnosis trends.
Clinicians should be aware that rising ASD and ADHD diagnosis rates likely reflect broader diagnostic criteria capturing individuals with lower average genetic liability, not a true increase in biologically distinct cases. This suggests that newly diagnosed patients—especially in recent years—may present with milder or more heterogeneous phenotypes, warranting individualized assessment rather than assumptions based on historical diagnostic profiles.
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