Nijmejer, Judith S.; Arias-Vasquez, Alejandro; Rommelse, Nanda N.J.; Altink, Marieke E.; Anney, Richard J.L.; Asherson, Philip; Banaschewski, Tobias; Buschgens, Cathelijne J.M.; Fliers, Ellen A.; Gill, Michael; Minderaa, Ruud B.; Poustka, Luise; Sergeant, Joseph A.; Buitelaar, Jan K.; Franke, Barbara; Ebstein, Richard P.; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sonuga-Barke, Edmund J.S.; Steinhausen, Hans-Christoph; Faraone, Stephen V.; Hartmann, Catharina A.; Hoekstra, Pieter J.:

Identifying Loci for the Overlap Between Attention-Deficit/Hyperactvity Disorder and Autism Spectrum Disorder Using a Genome-wide QTL Linkage Approach

In: Journal of the American Academy of Child and Adolescent Psychiatry, Jg. 49 (2010) ; Nr. 7, S. 675-685
ISSN: 0890-8567
Zeitschriftenaufsatz / Fach: Medizin
Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters
Abstract:
Objective—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.
Method—Participants of the International Multi-Center ADHD Genetics study comprising 1143
probands with ADHD and 1453 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 5407 autosomal single-nucleotide polymorphisms applying MERLIN-regress
software, both without and with inclusion of ADHD symptom scores as covariates.
Results—The analyses without ADHD symptom scores as covariates resulted in 3 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 & repetitive subscale, that on 15q
was found for the SCQ communication subscale, and that on 12q for the SCQ total score.
Conclusions—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.

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