Influences génétiques partagées entre les symptômes du TSA et du TDAH pendant le développement de l'enfant et de l'adolescent

Aperçu: G.M.

Influences génétiques partagées entre les symptômes de la DTS et du TDAH pendant le développement de l'enfant et de l'adolescent.

L'étude a exploré la continuité du chevauchement génétique entre les symptômes de la TSA et du TDAH dans un échantillon de population générale pendant l'enfance et l'adolescence ainsi que les liens unidirectionnels et transversaux des traits liés à la génétique du TDAH et au risque de TSA.

Les difficultés de communication sociale (N ≤ 5551, liste de contrôle des troubles sociaux et de la communication, SCDC) et les symptômes combinés du TDAH hyperactif-impulsif / inattentif (N ≤ 5678, Questionnaire sur les forces et les difficultés, SDQ-TDAH) ont été mesurés à plusieurs reprises dans une cohorte de naissance au Royaume-Uni (ALSPAC , Âgés de 7 à 17 ans).  

Dans la population générale, les influences génétiques pour les scores SCDC et SDQ-ADHD ont été partagées tout au long du développement. Les corrélations génétiques entre les traits ont atteint une force et une grandeur similaires (trait croisé rg ≤ 1, pmin = 3 × 10-4) comme ceux entre les mesures répétées du même trait (dans le trait rg ≤ 0,94, pmin = 7 × 10-4 ).

Dans la population générale, les étiologies génétiques entre les difficultés de communication sociale et les symptômes du TDAH sont partagées dans le développement de l'enfant et de l'adolescent et peuvent impliquer des voies biologiques similaires qui co-varient au cours du développement.  

À la fois dans la dimension TSA et TDAH, les traits basés sur la population sont également liés au trouble clinique, bien que des échantillons de recherche clinique beaucoup plus importants soient nécessaires pour détecter de manière fiable les relations trans-dimensionnelles des traits-trouble .  

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

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

Stergiakouli E¹, Davey Smith G², Martin J³, Skuse DH⁴, Viechtbauer W⁵, Ring SM², Ronald A⁶, Evans DE⁷, Fisher SE⁸, Thapar A⁹, St Pourcain B¹⁰.

Author information

1

grid.5337.2MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, Bristol, UK ; grid.5337.2School of Oral and Dental Sciences, University of Bristol, Bristol, UK.

2

grid.5337.2MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, Bristol, UK ; grid.5337.2School of Social and Community Medicine, University of Bristol, Bristol, UK.

3

grid.66859.34Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA USA ; grid.4714.6Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden ; grid.5600.3MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.

4

grid.83440.3bInstitute of Child Health, University College London, London, UK.

5

grid.5012.6Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands.

6

grid.88379.3dDepartment of Psychological Sciences, Birkbeck, University of London, London, UK.

7

grid.5337.2MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, Bristol, UK ; grid.1003.2University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Australia.

8

grid.419550.cLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands ; grid.5590.9Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.

9

grid.5600.3MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.

10

grid.5337.2MRC Integrative Epidemiology Unit (MRC IEU), University of Bristol, Bristol, UK ; grid.419550.cLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, 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.



PMID: 28392908

PMCID: PMC5379648

DOI: 10.1186/s13229-017-0131-2