title: Attention-deficit/hyperactivity disorder and comorbid disruptive behavior disorders: evidence of pleiotropy and new susceptibility loci.
abstract: 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.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3717, USA.
authors.forename: Mahim
authors.initials: M
authors.lastname: Jain
authors.forename: Luis Guillermo
authors.initials: LG
authors.lastname: Palacio
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Castellanos
authors.forename: Juan David
authors.initials: JD
authors.lastname: Palacio
authors.forename: David
authors.initials: D
authors.lastname: Pineda
authors.forename: Maria I
authors.initials: MI
authors.lastname: Restrepo
authors.forename: Juan F
authors.initials: JF
authors.lastname: Muñoz
authors.forename: Francisco
authors.initials: F
authors.lastname: Lopera
authors.forename: Deeann
authors.initials: D
authors.lastname: Wallis
authors.forename: Kate
authors.initials: K
authors.lastname: Berg
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.forename: Mauricio
authors.initials: M
authors.lastname: Arcos-Burgos
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology* / Q000235:genetics*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D015897:Comorbidity; D019955:Conduct Disorder / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics