title: Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development.
abstract: Shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) symptoms and autism spectrum disorder (ASD) symptoms have been reported. Cross-trait genetic relationships are, however, subject to dynamic changes during development. We investigated the continuity of genetic overlap between ASD and ADHD symptoms in a general population sample during childhood and adolescence. We also studied uni- and cross-dimensional trait-disorder links with respect to genetic ADHD and ASD risk.
  
  
  
  Social-communication difficulties (N≤ 5551, Social and Communication Disorders Checklist, SCDC) and combined hyperactive-impulsive/inattentive ADHD symptoms (N≤ 5678, Strengths and Difficulties Questionnaire, SDQ-ADHD) were repeatedly measured in a UK birth cohort (ALSPAC, age 7 to 17 years). Genome-wide summary statistics on clinical ASD (5305 cases; 5305 pseudo-controls) and ADHD (4163 cases; 12,040 controls/pseudo-controls) were available from the Psychiatric Genomics Consortium. Genetic trait variances and genetic overlap between phenotypes were estimated using genome-wide data.
  
  
  
  In the general population, genetic influences for SCDC and SDQ-ADHD scores were shared throughout development. Genetic correlations across traits reached a similar strength and magnitude (cross-traitrg≤ 1,pmin=3 × 10-4) as those between repeated measures of the same trait (within-traitrg≤ 0.94,pmin=7 × 10-4). Shared genetic influences between traits, especially during later adolescence, may implicate variants in K-RAS signalling upregulated genes (p-meta = 6.4 × 10-4). Uni-dimensionally, each population-based trait mapped to the expected behavioural continuum: risk-increasing alleles for clinical ADHD were persistently associated with SDQ-ADHD scores throughout development (marginal regressionR2= 0.084%). An age-specific genetic overlap between clinical ASD and social-communication difficulties during childhood was also shown, as per previous reports. Cross-dimensionally, however, neither SCDC nor SDQ-ADHD scores were linked to genetic risk for disorder.
  
  
  
  In the general population, genetic aetiologies between social-communication difficulties and ADHD symptoms are shared throughout child and adolescent development and may implicate similar biological pathways that co-vary during development. Within both the ASD and the ADHD dimension, population-based traits are also linked to clinical disorder, although much larger clinical discovery samples are required to reliably detect cross-dimensional trait-disorder relationships.
authors.affiliation: MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, Bristol, UK.|School of Oral and Dental Sciences, University of Bristol, Bristol, UK.
authors.forename: Evie
authors.initials: E
authors.lastname: Stergiakouli
authors.affiliation: MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA USA.|Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.|MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Martin
authors.affiliation: Institute of Child Health, University College London, London, UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Skuse
authors.affiliation: Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Viechtbauer
authors.affiliation: MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, Bristol, UK.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.affiliation: Department of Psychological Sciences, Birkbeck, University of London, London, UK.
authors.forename: Angelica
authors.initials: A
authors.lastname: Ronald
authors.affiliation: MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, Bristol, UK.|University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Australia.
authors.forename: David E
authors.initials: DE
authors.lastname: Evans
authors.affiliation: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
authors.forename: Simon E
authors.initials: SE
authors.lastname: Fisher
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
authors.forename: Anita
authors.initials: A
authors.lastname: Thapar
authors.affiliation: MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, Bristol, UK.|Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
authors.forename: Beate
authors.identifier: 0000-0002-4680-3517
authors.initials: B
authors.lastname: St Pourcain
mesh_terms: D000293:Adolescent; D041923:Adolescent Development; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002657:Child Development; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D066252:Sociological Factors; D011795:Surveys and Questionnaires; D006113:United Kingdom / Q000453:epidemiology
keywords: ADHD symptoms; ALSPAC; Clinical ADHD; Genetic overlap; Social communication