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

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

doi:10.1186/s13229-017-0131-2

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

Mol Autism. 2017 Apr 4:8:18. doi: 10.1186/s13229-017-0131-2. eCollection 2017.

Authors

Evie Stergiakouli^{1

2}, George Davey Smith^{1

3}, Joanna Martin^{4

5

6}, David H Skuse⁷, Wolfgang Viechtbauer⁸, Susan M Ring^{1

3}, Angelica Ronald⁹, David E Evans^{1

10}, Simon E Fisher^{11

12}, Anita Thapar⁶, Beate St Pourcain^{1

11}

Affiliations

¹ MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, Bristol, UK.
² School of Oral and Dental Sciences, University of Bristol, Bristol, UK.
³ School of Social and Community Medicine, University of Bristol, Bristol, UK.
⁴ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA USA.
⁵ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
⁶ MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
⁷ Institute of Child Health, University College London, London, UK.
⁸ Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands.
⁹ Department of Psychological Sciences, Birkbeck, University of London, London, UK.
¹⁰ University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Australia.
¹¹ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
¹² Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.

Abstract

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 R² = 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.

Keywords: ADHD symptoms; ALSPAC; Clinical ADHD; Genetic overlap; Social communication.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adolescent Development
Attention Deficit Disorder with Hyperactivity / diagnosis
Attention Deficit Disorder with Hyperactivity / epidemiology
Attention Deficit Disorder with Hyperactivity / genetics*
Attention Deficit Disorder with Hyperactivity / physiopathology
Autism Spectrum Disorder / diagnosis
Autism Spectrum Disorder / epidemiology
Autism Spectrum Disorder / genetics*
Autism Spectrum Disorder / physiopathology
Child
Child Development
Female
Genetic Variation
Genome-Wide Association Study
Humans
Male
Phenotype
Quantitative Trait, Heritable*
Risk Factors
Sociological Factors*
Surveys and Questionnaires
United Kingdom / epidemiology

Abstract

Publication types

MeSH terms

Grants and funding