title: Identifying loci for the overlap between attention-deficit/hyperactivity disorder and autism spectrum disorder using a genome-wide QTL linkage approach.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  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.
authors.affiliation: University Medical Center Groningen, Groningen, The Netherlands. j.nijmeijer@accare.nl
authors.forename: Judith S
authors.initials: JS
authors.lastname: Nijmeijer
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arias-Vásquez
authors.forename: Nanda N J
authors.initials: NN
authors.lastname: Rommelse
authors.forename: Marieke E
authors.initials: ME
authors.lastname: Altink
authors.forename: Richard J L
authors.initials: RJ
authors.lastname: Anney
authors.forename: Philip
authors.initials: P
authors.lastname: Asherson
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Cathelijne J M
authors.initials: CJ
authors.lastname: Buschgens
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Fliers
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Ruud B
authors.initials: RB
authors.lastname: Minderaa
authors.forename: Luise
authors.initials: L
authors.lastname: Poustka
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sergeant
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Richard P
authors.initials: RP
authors.lastname: Ebstein
authors.forename: Ana
authors.initials: A
authors.lastname: Miranda
authors.forename: Fernando
authors.initials: F
authors.lastname: Mulas
authors.forename: Robert D
authors.initials: RD
authors.lastname: Oades
authors.forename: Herbert
authors.initials: H
authors.lastname: Roeyers
authors.forename: Aribert
authors.initials: A
authors.lastname: Rothenberger
authors.forename: Edmund J S
authors.initials: EJ
authors.lastname: Sonuga-Barke
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Steinhausen
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Catharina A
authors.initials: CA
authors.lastname: Hartman
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Hoekstra
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D003142:Communication; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D006801:Humans; D008126:Lod Score; D008297:Male; D010552:Personality Assessment / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011594:Psychometrics / Q000706:statistics & numerical data; D040641:Quantitative Trait Loci / Q000235:genetics*; D012919:Social Behavior