Background
Attention-deficit/hyperactivity disorder (ADHD) comorbid with oppositional defiant
disorder (ODD) or conduct disorder (CD) and substance abuse/dependence seems to represent
a specific subset within the phenotypic ADHD spectrum.
Methods
We applied complex segregation and linkage analyses in a set of multigenerational
families densely segregating ADHD comorbid with ODD, CD, alcohol abuse/dependence,
and nicotine dependence.
Results
Our data suggest that ADHD cosegregates with disruptive behaviors as a unique, phenotypically
variable trait as evidenced by highly significant pair-wise linkages among: ADHD and
ODD (logarithm of odds [LOD] = 14.19), ADHD and CD (LOD = 5.34), ODD and CD (LOD =
6.68), and CD and alcohol abuse/dependence (LOD = 3.98). In addition to previously
reported ADHD susceptibility loci, we found evidence of linkage for comorbid ADHD
phenotypes to loci at 8q24, 2p21-22.3, 5p13.1-p13.3, 12p11.23-13.3, 8q15, and 14q21.1-22.2.
These results were replicated with an affected status phenotype derived from latent
class clusters.
Conclusions
Patterns of cosegregation of ADHD with comorbidities can inform our understanding
of the inheritance patterns not only of ADHD but also of disruptive behavioral disorders
and alcohol abuse/dependence. Refining the comorbid ADHD phenotype by determining
the cosegregation profile of specific comorbidities might be a powerful tool for defining
significant regions of linkage.
Key Words
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Article info
Publication history
Published online: September 04, 2006
Accepted:
June 14,
2006
Received in revised form:
May 22,
2006
Received:
February 17,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
