Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families

J Autism Dev Disord. 2021 Jan;51(1):276-285. doi: 10.1007/s10803-020-04552-x.

Abstract

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly heritable neurodevelopmental disorders that frequently co-occur. Both rare and common genetic variants are important for ASD and ADHD risk but their combined contribution to clinical heterogeneity is unclear. In a sample of 39 ASD and/or ADHD families we estimated the overall variance explained by known rare copy number variants (CNVs) and polygenic risk score (PRS) from common variants to be 10% in comorbid ASD/ADHD, 4% in ASD and 2% in ADHD. We show that burden of large, rare CNVs and PRS is significantly higher in adult ASD and/or ADHD patients with sustained need for specialist care compared to their unaffected relatives, while affected relatives fall in-between the two.

Keywords: Attention deficit/hyperactivity disorder; Autism spectrum disorder; Comorbidity; Copy number variants; Families; Polygenic risk score.

MeSH terms

  • Adolescent
  • Adult
  • Attention Deficit Disorder with Hyperactivity / diagnosis*
  • Attention Deficit Disorder with Hyperactivity / epidemiology
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Autistic Disorder / diagnosis*
  • Autistic Disorder / epidemiology
  • Autistic Disorder / genetics*
  • Child
  • Comorbidity
  • DNA Copy Number Variations / genetics*
  • Denmark / epidemiology
  • Female
  • Humans
  • Male
  • Multifactorial Inheritance / genetics*
  • Predictive Value of Tests
  • Risk Factors