title: Shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) traits in children and clinical ADHD.
abstract: OBJECTIVE
  Twin studies and genome-wide complex trait analysis (GCTA) are not in agreement regarding heritability estimates for behavioral traits in children from the general population. This has sparked a debate on the possible difference in genetic architecture between behavioral traits and psychiatric disorders. In this study, we test whether polygenic risk scores associated with variation in attention-deficit/hyperactivity disorder (ADHD) trait levels in children from the general population predict ADHD diagnostic status and severity in an independent clinical sample.
  
  
  METHODS
  Single nucleotide polymorphisms (SNPs) with p < .5 from a genome-wide association study of ADHD traits in 4,546 children (mean age, 7 years 7 months) from the Avon Longitudinal Study of Parents and Children (ALSPAC; general population sample) were selected to calculate polygenic risk scores in 508 children with an ADHD diagnosis (independent clinical sample) and 5,081 control participants. Polygenic scores were tested for association with case-control status and severity of disorder in the clinical sample.
  
  
  RESULTS
  Increased polygenic score for ADHD traits predicted ADHD case-control status (odds ratio = 1.17 [95% CI = 1.08-1.28], p = .0003), higher ADHD symptom severity (β = 0.29 [95% CI = 0.04-0.54], p = 0.02), and symptom domain severity in the clinical sample.
  
  
  CONCLUSIONS
  This study highlights the relevance of additive genetic variance in ADHD, and provides evidence that shared genetic factors contribute to both behavioral traits in the general population and psychiatric disorders at least in the case of ADHD.
authors: Medical Research Centre (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK. Electronic address: e.stergiakouli@bristol.ac.uk.
authors: Evie
authors: E
authors: Stergiakouli
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
authors: Joanna
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: Marian L
authors: ML
authors: Hamshere
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK; School of Psychology, College of Biomedical and Life Sciences, Cardiff University.
authors: Kate
authors: K
authors: Langley
authors: Medical Research Centre (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK; University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors: David M
authors: DM
authors: Evans
authors: Medical Research Centre (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK; School of Oral and Dental Sciences, University of Bristol, and the School of Experimental Psychology, University of Bristol.
authors: Beate
authors: B
authors: St Pourcain
authors: Medical Research Centre (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
authors: Nicholas J
authors: NJ
authors: Timpson
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
authors: Michael J
authors: MJ
authors: Owen
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.
authors: Michael
authors: M
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: Anita
authors: A
authors: Thapar
authors: Medical Research Centre (MRC) Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, UK.
authors: George
authors: G
authors: Davey Smith
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D006113:United Kingdom
keywords: Avon Longitudinal Study of Parents and Children (ALSPAC); attention-deficit/hyperactivity disorder (ADHD); common variants; genetics; polygenic risk scores