Identifying Loci for the Overlap Between ADHD and ASD Using a Genome-wide QTL Linkage Approach

Nijmeijer, JS, Arias-Vasquez, A, Rommelse, NNJ, Altink, ME, Anney, R, Asherson, P, Banaschewski, T, Buschgens, CJM, Fliers, EA, Gill, M, Minderaa, RB, Poustka, L, Sergeant, JA, Buitelaar, JK, Franke, B, Ebstein, RP, Miranda, A, Oades, RD, Roeyers, H, Rothenberger, A, Sonuga-Barke, E, Steinhausen, HC, Faraone, SV, Hartman, CA and Hoekstra, PJ (2010) Identifying Loci for the Overlap Between ADHD and ASD Using a Genome-wide QTL Linkage Approach. Journal of the American Academy of Child and Adolescent Psychiatry, 49 (7), 675-685.

Abstract

Background: Recent studies in the general population and clinical samples have shown that Pervasive Developmental Disorder (PDD) and Attention-Deficit/Hyperactivity Disorder (ADHD) overlap, both in symptoms and in underlying genetic influences.

Objectives: In this study, the genetic basis for PDD symptoms in children with ADHD was addressed using a Quantitative Trait Locus linkage approach.

Methods: Genome wide linkage analyses were performed in the Dutch participants of the International Multi-Center ADHD Genetics (IMAGE) study comprising 365 DSM-IV combined type ADHD probands and 439 of their siblings who were part of 365 families. The total and subscale scores of the Children’s Social Behavior Questionnaire (CSBQ; a measure of subtle PDD symptoms) with heritabilities >0.2 were used as quantitative traits. A total of 5407 autosomal single-nucleotide polymorphisms (SNPs) were used to run multipoint regression-based linkage analyses using MERLIN-regress software.

Results: Suggestive linkage signals (LOD? 2.0) were found on chromosomes 2q, 3p, 7p, 7q, and 8p. The signal on chromosome 7q11.2 overlapped for three CSBQ scales, namely the total score (LOD 2.08), and the scales addressing withdrawn behavior (LOD 3.07) and understanding of social information (LOD 2.01), respectively. The regions on chromosome 7q11 and 8p21 that we identified have previously been found for autism, and the chromosome 7p13 finding overlaps with a linkage study for ADHD.

Conclusions: Defining an ADHD subtype with PDD symptoms appears to be a valuable approach for detecting susceptibility loci for the overlap between ADHD and PDD

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