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Identifying loci for the overlap between attention-deficit/hyperactivity disorder and autism spectrum disorder using a genome-wide QTL linkage approach.

ABSTRACT: The genetic basis for autism spectrum disorder (ASD) symptoms in children with attention-deficit/hyperactivity disorder (ADHD) was addressed using a genome-wide linkage approach.Participants of the International Multi-Center ADHD Genetics study comprising 1,143 probands with ADHD and 1,453 siblings were analyzed. The total and subscale scores of the Social Communication Questionnaire (SCQ) were used as quantitative traits for multipoint regression-based linkage analyses on 5,407 autosomal single-nucleotide polymorphisms applying MERLIN-regress software, both without and with inclusion of ADHD symptom scores as covariates.The analyses without ADHD symptom scores as covariates resulted in three suggestive linkage signals, i.e., on chromosomes 15q24, 16p13, and 18p11. Inclusion of ADHD symptom scores as covariates resulted in additional suggestive loci on chromosomes 7q36 and 12q24, whereas the LOD score of the locus on chromosome 15q decreased below the threshold for suggestive linkage. The loci on 7q, 16p, and 18p were found for the SCQ restricted and repetitive subscale, that on 15q was found for the SCQ communication subscale, and that on 12q for the SCQ total score.Our findings suggest that QTLs identified in this study are ASD specific, although the 15q QTL potentially has pleiotropic effects for ADHD and ASD. This study confirms that genetic factors influence ASD traits along a continuum of severity, as loci potentially underlying ASD symptoms in children with ADHD were identified even though subjects with autism had been excluded from the IMAGE sample, and supports the hypothesis that differential genetic factors underlie the three ASD dimensions.

SUBMITTER: Nijmeijer JS

PROVIDER: S-EPMC2929476 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Identifying loci for the overlap between attention-deficit/hyperactivity disorder and autism spectrum disorder using a genome-wide QTL linkage approach.

Nijmeijer Judith S JS Arias-Vásquez Alejandro A Rommelse Nanda N J NN Altink Marieke E ME Anney Richard J L RJ Asherson Philip P Banaschewski Tobias T Buschgens Cathelijne J M CJ Fliers Ellen A EA Gill Michael M Minderaa Ruud B RB Poustka Luise L Sergeant Joseph A JA Buitelaar Jan K JK Franke Barbara B Ebstein Richard P RP Miranda Ana A Mulas Fernando F Oades Robert D RD Roeyers Herbert H Rothenberger Aribert A Sonuga-Barke Edmund J S EJ Steinhausen Hans-Christoph HC Faraone Stephen V SV Hartman Catharina A CA Hoekstra Pieter J PJ

Journal of the American Academy of Child and Adolescent Psychiatry 20100520 7

<h4>Objective</h4>The genetic basis for autism spectrum disorder (ASD) symptoms in children with attention-deficit/hyperactivity disorder (ADHD) was addressed using a genome-wide linkage approach.<h4>Method</h4>Participants of the International Multi-Center ADHD Genetics study comprising 1,143 probands with ADHD and 1,453 siblings were analyzed. The total and subscale scores of the Social Communication Questionnaire (SCQ) were used as quantitative traits for multipoint regression-based linkage a ...[more]

PMID: 20610137

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Project description:Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD) are two of the most represented neurodevelopmental conditions in childhood. The diagnostic shift introduced by the DSM-5, allowing a combined diagnosis of ADHD and ASD, poses different clinical challenges related to diagnostic overshadowing, accuracy of clinical judgment and potential delay in an ASD diagnosis in children presenting with ADHD. Here we tried to disentangle the clinical phenotype and specificity of the two co-occurring conditions in relation to autism traits and empathy, by comparing children with ASD with and without comorbid ADHD with children presenting ADHD only and children with typical development. The child versions of the Autism Quotient (C-AQ) and Empathy Quotient (C-EQ) were administered to a total sample of 198 male children between 6 and 14 years old with age appropriate language skills and normal intelligence. Univariate analysis demonstrated no significant differences in the C-AQ total and subscale scores as well as the C-EQ between children with ASD and children with ASD + ADHD, while children with ADHD alone presented an intermediate phenotype between ASD and TD. Furthermore, a receiver operating characteristic (ROC) analysis was applied to discriminate among the different phenotypes. We found that the C-AQ and C-EQ were accurate at distinguishing with satisfactory reliability between: (a) ASD vs. non- ASD (N-ASD) groups comprising both ADHD and TD children (Area Under the Curve AUC 88% for C-AQ and 81% for C-EQ); (b) ASD and TD (AUC 92% for C-AQ and 95% for C-EQ); (c) ASD and ADHD (AUC 80% for C-AQ and 68% for C-EQ). Our data confirm the reliability of the C-AQ and C-EQ as behavioral markers to differentiate ASD (regardless of comorbid ADHD) from an ADHD condition and TD. Interestingly, in our sample an ADHD condition does not increase the severity of the clinical phenotype in terms of autism traits distribution and empathy, suggesting that the psychological measures detected by the two quantitative instruments are independent of ADHD traits. This evidence will contribute to the translational efforts in developing better tailored treatments and preventive strategies.

Project description:BackgroundFor the diagnosis of attention-deficit/hyperactivity disorder (ADHD), the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) proposes that adherence to six symptoms in either group (inattention and hyperactivity/impulsivity) will lead to the diagnosis of one of three presentations of the disorder. Underlying this diagnostic algorithm is the assumption that the 18 symptoms have equal relevance for the diagnosis of ADHD, all are equally severe, and all have the same power to detect the presence of the disorder in all its degrees of severity, without considering the possibility of using marker symptoms. However, several studies have suggested that ADHD symptoms differ in both their power to discriminate the presence of the disorder and the degree of severity they represent. The aim of the present study was to replicate the results of previous research by evaluating the discriminative capacity and relative severity of ADHD symptoms, as well as to extend the investigation of this topic to Spanish-speaking Latin American samples.MethodsThe properties of ADHD symptoms rated by the parents of 474 Chilean children were analyzed. Symptom parameters were estimated using the graded response model.ResultsThe results suggest that symptoms of ADHD differ substantially in both the accuracy with which they reflect the presence of the disorder, and their relative severity. Symptoms "easily distracted by extraneous stimuli" and "have difficulty sustaining attention in tasks" (inattention) and "is on the go, acting as if driven by motor" (hyperactivity/impulsivity) were the most informative, and those with relatively lower severity thresholds.DiscussionThe fact that symptoms differ substantially in the probability of being observed conditionally to the trait level suggests the need to refine the diagnostic process by weighting the severity of the symptom, and even to assess the possibility of defining ADHD marker symptoms, as has been done in other disorders.

Dataset Information

Identifying loci for the overlap between attention-deficit/hyperactivity disorder and autism spectrum disorder using a genome-wide QTL linkage approach.

Publications

Identifying loci for the overlap between attention-deficit/hyperactivity disorder and autism spectrum disorder using a genome-wide QTL linkage approach.

Similar Datasets

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