Associating psychiatric polygenic risk scores with neurodevelopmental disorders in a clinical child and adolescent sample

Objective: Psychiatric disorders like attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and schizophrenia (SCZ) are highly heritable and influenced by many single nucleotide polymorphisms (SNPs).... [ view full abstract ]

Objective: Psychiatric disorders like attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and schizophrenia (SCZ) are highly heritable and influenced by many single nucleotide polymorphisms (SNPs). One way to explore the influence of common genetic variation is the use of polygenic risk scores (PRS), an individual’s genetic risk for a disorder. We aim to identify associations of genetic risk for ADHD, ASD and SCZ, with neurodevelopmental disorders (NDD) in a clinical child and adolescent population.

Methods: We derived PRS for ADHD, ASD and SCZ using the latest GWAS results, and tested for an association in a sample 1) with a single diagnosis of ADHD (N=280), 2) with a single diagnosis of ASD (N=295), and 3) combining the first two samples, thus subjects with either ASD or ADHD, plus children with both diagnoses (NDD, N=688). With logistic regression analyses we explored associations between each clinical sample and a sample of healthy controls (N=957). Follow-up analyses exploring the associations further were performed by means of linear regression analyses of the syndrome scales of the child behavioral checklist (CBCL) in each clinical sample.

Results: Our results showed a significant association of the ADHD PRS with ADHD (P=7.2x10^-5, OR=1.37), and with NDD (P=1.44x10^-4, OR=1.32), but not with ASD status (P=5.04x10^-2, OR=1.23). No associations with the ASD and SCZ PRS were observed. Follow-up analyses with the ADHD PRS and CBCL syndrome-scales showed in the ADHD sample associations with anxious/depressed (Beta=0.119, P=0.035) and a trend towards aggressive behavior (Beta=0.111, P=0.054). In the NDD sample an association with attention problems (Beta=0.093, P=0.035) and aggressive behavior (Beta=0.107, P=0.015) was observed.

Conclusion: The genetic risk of ADHD is significantly associated with ADHD in a clinical child and adolescent sample. The signal can be traced back to attention problems and aggressive behavior in the complete NDD sample but replication in larger samples is needed to confirm these results.