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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Molecular Autism 1/2017

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

Zeitschrift:
Molecular Autism > Ausgabe 1/2017
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13229-017-0131-2) contains supplementary material, which is available to authorized users.

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 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.
Zusatzmaterial
Additional file 1: Additional note. Selection of SDQ-ADHD measures. Additional note. Meta-analysis of correlated test statistics from pathway analysis. Additional note. Additional references. Additional note. Web resources. Table S1. Descriptives of SDQ-ADHD and SCDC scores in ALSPAC. Table S2. Phenotypic correlations of SDQ-ADHD scores in ALSPAC. Table S3. Phenotypic correlations of SCDC scores in ALSPAC. Table S4. Univariate GREML of SDQ-ADHD scores in ALSPAC. Table S5. Univariate GREML of SCDC scores in ALSPAC. Table S6. Bivariate GREML of SDQ-ADHD scores in ALSPAC. Table S7. Bivariate GREML of SCDC scores in ALSPAC. Table S8. Bivariate GREML and Pearson correlations of SDQ-ADHD and SCDC scores in ALSPAC. Table S10. Association between ADHD polygenic scores and SDQ-ADHD scores in ALSPAC. Table S11. Association between ASD polygenic scores and SDQ-ADHD scores in ALSPAC. Table S12. Association between ADHD polygenic scores and SCDC scores in ALSPAC. (DOCX 92 kb)
13229_2017_131_MOESM1_ESM.docx
Additional file 2: Table S9. Pathway-based dissection of additive genetic variance in SDQ-ADHD and SCDC scores according to 50 molecular signatures database hallmark gene set collections. (XLSX 20 kb)
13229_2017_131_MOESM2_ESM.xlsx
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