Journal Article

Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development

Ronald, Angelica, Stergiakouli, Evie, Davey Smith, George, Viechtbauer, Wolfgang, Ring, Susan M., Thapar, Anita, Fisher, Simon E., St Pourcain, Beate, Martin, Joanna, Skuse, David H., Evans, David E.

2017

Overview

Background 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. Methods 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. Results 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-trait r g  ≤ 1, p min   =  3 × 10 −4 ) as those between repeated measures of the same trait (within-trait r g  ≤ 0.94, p min   =  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 regression R 2  = 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. Conclusions 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.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: ADHD symptoms / Adolescent / Adolescent Development / ALSPAC / Attention Deficit Disorder with Hyperactivity - diagnosis / Attention Deficit Disorder with Hyperactivity - epidemiology / Attention Deficit Disorder with Hyperactivity - genetics / Attention Deficit Disorder with Hyperactivity - physiopathology / Attention deficit hyperactivity disorder / Autism Spectrum Disorder - diagnosis / Autism Spectrum Disorder - epidemiology / Autism Spectrum Disorder - genetics / Autism Spectrum Disorder - physiopathology / Autistic children / Child / Child Development / Clinical ADHD / Female / Genetic overlap / Genetic Variation / Genome-Wide Association Study / Human Genetics / Humans / Hyperactivity / Male / Medicine / Medicine & Public Health / Methods / Neurology / Neuropsychology / Neurosciences / Pediatrics / Phenotype / Psychiatry / Quantitative Trait, Heritable / Risk Factors / Social communication / Sociological Factors / Studies / Surveys and Questionnaires / Teenagers / United Kingdom - epidemiology