title: Linkage and association analysis of ADHD endophenotypes in extended and multigenerational pedigrees from a genetic isolate.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is a heritable, chronic, neurodevelopmental disorder with serious long-term repercussions. Despite being one of the most common cognitive disorders, the clinical diagnosis of ADHD is based on subjective assessments of perceived behaviors. Endophenotypes (neurobiological markers that cosegregate and are associated with an illness) are thought to provide a more powerful and objective framework for revealing the underlying neurobiology than syndromic psychiatric classification. Here, we present the results of applying genetic linkage and association analyses to neuropsychological endophenotypes using microsatellite and single nucleotide polymorphisms. We found several new genetic regions linked and/or associated with these endophenotypes, and others previously associated to ADHD, for example, loci harbored in the LPHN3, FGF1, POLR2A, CHRNA4 and ANKFY1 genes. These findings, when compared with those linked and/or associated to ADHD, suggest that these endophenotypes lie on shared pathways. The genetic information provided by this study offers a novel and complementary method of assessing the genetic causes underpinning the susceptibility to behavioral conditions and may offer new insights on the neurobiology of the disorder.
authors.affiliation: Genomics and Predictive Medicine, Genome Biology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, Australia.
authors.forename: C A
authors.initials: CA
authors.lastname: Mastronardi
authors.affiliation: Genomics and Predictive Medicine, Genome Biology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Pillai
authors.affiliation: Group of Neurosciences, University of Antioquia, Medellin, Colombia.
authors.forename: D A
authors.initials: DA
authors.lastname: Pineda
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Martinez
authors.affiliation: Group of Neurosciences, University of Antioquia, Medellin, Colombia.
authors.forename: F
authors.initials: F
authors.lastname: Lopera
authors.affiliation: Genomics and Predictive Medicine, Genome Biology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, Australia.
authors.forename: J I
authors.initials: JI
authors.lastname: Velez
authors.affiliation: Group of Neurosciences, University of Antioquia, Medellin, Colombia.
authors.forename: J D
authors.initials: JD
authors.lastname: Palacio
authors.affiliation: Genomics and Predictive Medicine, Genome Biology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Patel
authors.affiliation: National Center for Indigenous Genomics, Genome Biology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Easteal
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Acosta
authors.affiliation: The NYU Child Study Center at NYU Langone Medical Center, New York, NY, US and Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, US.
authors.forename: F X
authors.initials: FX
authors.lastname: Castellanos
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Muenke
authors.affiliation: Genomics and Predictive Medicine, Genome Biology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, Australia.|Group of Neurosciences, University of Antioquia, Medellin, Colombia.|Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Arcos-Burgos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D003072:Cognition Disorders / Q000235:genetics; D003105:Colombia; D058068:Endophenotypes / Q000032:analysis*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009483:Neuropsychological Tests; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics