Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is a genetically influenced brain disorder with a prevalence of 3-5% in school-age children. Affected sibling pairs and densely affected multi-generation families have been recruited from Colombia, South America, the US, and Germany. A genome-wide search for loci linked to ADHD has been completed and we have identified at least five regions in the human genome that contain genes to may contribute to ADHD (Arcos-Burgos et al. 2004). To date, we have complete clinical information on a total of over 600 small and large, multi-generation families, respectively (Palacio et al., 2004;Jain et al. 2006). We are now in the process to use the clinical and genome data to search for genes that contribute to ADHD. Recently, we have identified a gene that has the highest genetic contribution to ADHD to date. In the world-wide samples statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology and treatment of ADHD (Arcos-Burgos et al. 2010).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHG000175-11
Application #
8149422
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2010
Total Cost
$1,313,396
Indirect Cost

  Institution

Name
National Human Genome Research Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Swanson, James M; Arnold, L Eugene; Molina, Brooke S G et al. (2017) Young adult outcomes in the follow-up of the multimodal treatment study of attention-deficit/hyperactivity disorder: symptom persistence, source discrepancy, and height suppression. J Child Psychol Psychiatry 58:663-678
Mastronardi, C A; Pillai, E; Pineda, D A et al. (2016) Linkage and association analysis of ADHD endophenotypes in extended and multigenerational pedigrees from a genetic isolate. Mol Psychiatry 21:1434-40
Acosta, Maria T; Swanson, James; Stehli, Annamarie et al. (2016) ADGRL3 (LPHN3) variants are associated with a refined phenotype of ADHD in the MTA study. Mol Genet Genomic Med 4:540-7
Martinez, Ariel F; Abe, Yu; Hong, Sungkook et al. (2016) An Ultraconserved Brain-Specific Enhancer Within ADGRL3 (LPHN3) Underpins Attention-Deficit/Hyperactivity Disorder Susceptibility. Biol Psychiatry 80:943-954
Walsh, Karin S; Velez, Jorge I; Kardel, Peter G et al. (2013) Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1. Dev Med Child Neurol 55:131-8
Fallgatter, Andreas J; Ehlis, Ann-Christine; Dresler, Thomas et al. (2013) Influence of a Latrophilin 3 (LPHN3) risk haplotype on event-related potential measures of cognitive response control in attention-deficit hyperactivity disorder (ADHD). Eur Neuropsychopharmacol 23:458-68
Volkow, Nora D; Muenke, Maximilian (2012) The genetics of addiction. Hum Genet 131:773-7
Acosta, Maria T; Bearden, Carrie E; Castellanos, F Xavier et al. (2012) The Learning Disabilities Network (LeaDNet): using neurofibromatosis type 1 (NF1) as a paradigm for translational research. Am J Med Genet A 158A:2225-32
Arcos-Burgos, Mauricio; Velez, Jorge I; Solomon, Benjamin D et al. (2012) A common genetic network underlies substance use disorders and disruptive or externalizing disorders. Hum Genet 131:917-29
Arcos-Burgos, Mauricio; Londono, Ana C; Pineda, David A et al. (2012) Analysis of brain metabolism by proton magnetic resonance spectroscopy (1H-MRS) in attention-deficit/hyperactivity disorder suggests a generalized differential ontogenic pattern from controls. Atten Defic Hyperact Disord 4:205-12

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