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

Stergiakouli, Evie, Davey Smith, George, Martin, Joanna, Skuse, David H., Viechtbauer, Wolfgang, Ring, Susan M., Ronald, Angelica, Evans, David E., Fisher, Simon E., Thapar, Anita and St Pourcain, Beate (2017) Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development. Molecular Autism, 8 1: . doi:10.1186/s13229-017-0131-2

Author Stergiakouli, Evie
Davey Smith, George
Martin, Joanna
Skuse, David H.
Viechtbauer, Wolfgang
Ring, Susan M.
Ronald, Angelica
Evans, David E.
Fisher, Simon E.
Thapar, Anita
St Pourcain, Beate
Title Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development
Journal name Molecular Autism   Check publisher's open access policy
ISSN 2040-2392
Publication date 2017-04-01
Year available 2017
Sub-type Article (original research)
DOI 10.1186/s13229-017-0131-2
Open Access Status DOI
Volume 8
Issue 1
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2018
Language eng
Formatted 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 rg ≤ 1, pmin = 3 × 10−4) as those between repeated measures of the same trait (within-trait rg ≤ 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 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.
Keyword ADHD symptoms
Clinical ADHD
Genetic overlap
Social communication
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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UQ Diamantina Institute Publications
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