Association of attention-deficit/hyperactivity disorder with a candidate region for reading disabilities on chromosome 6p.
BACKGROUND
Reading disabilities (RD) and attention-deficit hyperactivity/disorder (ADHD) are two common childhood disorders that co-occur by chance more often than expected. Twin studies and overlapping genetic linkage findings indicate that shared genetic factors partially contribute to this comorbidity. Linkage of ADHD to 6p, an identified RD candidate locus, has previously been reported, suggesting the possibility of a pleiotropic gene at this locus. RD has been previously associated with five genes in the region, particularly DCDC2 and KIAA0319.


METHODS
To test whether these genes also contribute to ADHD, we investigated markers previously associated with RD for association with ADHD and ADHD symptoms in a sample of families with ADHD (n = 264). Markers were located in two subregions, VMP/DCDC2 and KIAA0319/TTRAP.


RESULTS
Across all analyses conducted, strong evidence for association was observed in the VMP/DCDC2 region. Association was equally strong with symptoms of both inattention and hyperactivity/impulsivity, suggesting that this locus contributes to both symptom dimensions. Markers were also tested for association with measures of reading skills (word identification, decoding); however, there was virtually no overlap in the markers associated with ADHD and those associated with reading skills in this sample.


CONCLUSIONS
Overall this study supports a previous linkage study of ADHD indicating a risk gene for ADHD on 6p and points to VMP or DCDC2 as the most likely candidates.
Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Canada.
Jillian M
JM
Couto
Lissette
L
Gomez
Karen
K
Wigg
Abel
A
Ickowicz
Tejaswee
T
Pathare
Molly
M
Malone
James L
JL
Kennedy
Russell
R
Schachar
Cathy L
CL
Barr
D000293:Adolescent; D001288:Attention / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics*; D002648:Child; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004268:DNA-Binding Proteins; D004410:Dyslexia / Q000150:complications / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010727:Phosphoric Diester Hydrolases; D011932:Reading; D014157:Transcription Factors / Q000235:genetics
C510451:DCDC2 protein, human; D004268:DNA-Binding Proteins; D005819:Genetic Markers; C500377:KIAA0319 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C046375:NRSN1 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D010727:Phosphoric Diester Hydrolases; C474866:TDP2 protein, human