Identifying loci for the overlap between attention-deficit/hyperactivity disorder and autism spectrum disorder using a genome-wide QTL linkage approach.
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.
Nijmeijer
Judith S
JS
University Medical Center Groningen, Groningen, The Netherlands. j.nijmeijer@accare.nl
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
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