Changes in Genetic Contributions to ASD and ADHD by Year of Diagnosis

Vollständiger Abstract

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Importance The incidences of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have increased markedly over recent decades, raising concerns about the emergence of new risk factors. Current literature typically attributes increased rates to changes in diagnostic practice, stigmatization, and awareness, but critically few studies have explored changes in underlying risk factors. Objective To assess changes in the genetic risk profile of individuals diagnosed with ASD or ADHD by year of incident diagnosis and explore results in comparison with those expected under simulated scenarios. Design, Setting, and Participants This cohort study used data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH2015) study, a population-based case-cohort in Denmark among individuals with incident diagnoses for ASD and ADHD made from 1994 to 2016. Data were analyzed from January 2024 until September 2025. Exposure Year of incident diagnosis. Regression models tested changes in the mean genetic risk profile of individuals diagnosed in each consecutive year (1994-2016), adjusting for age, sex, and ancestry. Main Outcomes Polygenic scores for psychiatric (ADHD, ASD, depression, bipolar, and schizophrenia) and cognitive-behavioral (addiction, educational attainment, IQ, neuroticism, and risk-taking) outcomes were used to capture genetic risk profiles of diagnosed individuals. Empirical trends were compared with those expected under different simulated drivers of increasing rates. Results A total of 17 071 individuals with incident diagnoses for ASD (4196 female [24.6%]; mean [SD] age at diagnosis, 9.7 [4.6] years) and 20 111 with diagnoses for ADHD (5960 female [29.6%]; mean [SD] age at diagnosis, 11.0 ([4.7] years) were analyzed. A more recent ADHD diagnosis was associated with decreased genetic risk for ADHD as shown by difference in mean polygenic score (β estimate per 10-year increase, −0.06 SDs; 95% CI, −0.09 to −0.03 SDs; P = .001) and other disorders, including ASD, bipolar, and schizophrenia (eg, ASD: β per 10-year increase, −0.07 SDs; 95% CI, −0.10 to −0.03 SDs; P < .001). Similarly, a more recent ASD diagnosis was associated with decreased genetic risk for ASD (β per 10-year increase, −0.07 SDs; 95% CI, −0.10 to −0.04 SDs; P < .001) and other disorders and traits, including bipolar disorder, schizophrenia, and educational attainment (eg, bipolar disorder: β per 10-year increase, −0.05 SDs; 95% CI, −0.08 to −0.02 SDs; P = .001). Conclusions and Relevance By analyzing multiple polygenic scores together with simulated expectations, this study could disambiguate among competing hypotheses about scenarios that may be associated with increased rates of ADHD and ASD diagnoses. Findings support broadening diagnostic criteria as an explanation for increasing rates, with implications for understanding changes in risk factors and clinical practice.