title: The relative contribution of common and rare genetic variants to ADHD.
abstract: Attention deficit hyperactivity disorder (ADHD) is highly heritable. Genome-wide molecular studies show an increased burden of large, rare copy-number variants (CNVs) in children with ADHD compared with controls. Recent polygenic risk score analyses have also shown that en masse common variants are enriched in ADHD cases compared with population controls. The relationship between these common and rare variants has yet to be explored. In this study, we tested whether children with ADHD with (N=60) a large (>500 kb), rare (<1% frequency) CNV differ by polygenic risk scores for ADHD to children with ADHD without such CNVs (N=421). We also compared ADHD polygenic scores in ADHD children with and without CNVs with a group of population controls (N=4670; of whom N=397 had CNVs). The results show that children with ADHD with large, rare CNVs have lower polygenic scores than children without such CNVs (odds ratio (OR)=0.73, P=0.023). Although ADHD children without CNVs had higher scores than controls (OR=1.18, P=0.0031), this difference was not observed for ADHD children with CNVs (OR=0.86, P=0.27). These results are consistent with a polygenic liability threshold model of ADHD with both common and rare variants involved.
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
authors: J
authors: 0000000289113479
authors: J
authors: Martin
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
authors: M C
authors: MC
authors: O'Donovan
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
authors: A
authors: A
authors: Thapar
authors: 1] MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK [2] School of Psychology, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK.
authors: K
authors: K
authors: Langley
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
authors: N
authors: N
authors: Williams
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide