A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication

Autor: William A. Gahl, Juan David Palacio, Josep Antoni Ramos-Quiroga, Stephen V. Faraone, Francisco X. Castellanos, David Pineda, Maximilian Muenke, Joan Z. Balog, Christiane Seitz, Deeann Wallis, Hakon Hakonarson, Andres Arbelaez, Christian Jacob, Horia Stanescu, James M. Swanson, Marta Ribasés, K.P. Lesch, Robert Kleta, Brion S. Maher, Jasmin Romanos, Jayaprakash D. Karkera, Vortmeyer A, Francisco Lopera, Mahim Jain, Robert Long, Maria Teresa Acosta, A. Hervas, U. Hemminger, Marcel Romanos, Sabina Domené, Tobias J. Renner, Miguel Casas, Per M. Knappskog, Ana C. Londoño, Jan Haavik, Haukur Palmason, Susanne Walitza, Mauricio Arcos-Burgos, Shively S, Joan E. Bailey-Wilson, Mònica Bayés, Bru Cormand, Josephine Elia, Andreas Warnke, Kate Berg, Jorge I. Vélez, Christine M. Freitag, Stefan Johansson, Lie J, Erich Roessler, Jobst Meyer
Přispěvatelé: University of Zurich, Muenke, M
Rok vydání: 2010
Předmět:
Male
Magnetic Resonance Spectroscopy
LPHN3
Genetic Linkage
2804 Cellular and Molecular Neuroscience
Ciencias de la Salud
Genome
Receptors
G-Protein-Coupled
2738 Psychiatry and Mental Health
Latrophilin 3
Child
Genetics
education.field_of_study
Brain
Chromosome Mapping
COMPLEX TRAIT
10058 Department of Child and Adolescent Psychiatry
Otras Ciencias de la Salud
Psychiatry and Mental health
Child
Preschool
Female
purl.org/becyt/ford/3 [https]
Adult
CIENCIAS MÉDICAS Y DE LA SALUD
Adolescent
Genotype
Receptors
Peptide
GENETICS
Cell Survival
Population
610 Medicine & health
Biology
purl.org/becyt/ford/3.3 [https]
Cellular and Molecular Neuroscience
Neuroimaging
mental disorders
1312 Molecular Biology
Humans
ADHD
Genetic Predisposition to Disease
education
Molecular Biology
Gene
Genetic association
Linkage (software)
Polymorphism
Genetic
Heritability
GENE
LATROPHILIN
Attention Deficit Disorder with Hyperactivity
Central Nervous System Stimulants
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
DOI: 10.5167/uzh-31561
Popis: Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five samples from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide samples (total n6360, with 2627 ADHD cases and 2531 controls) 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. Fil: Arcos Burgos, M.. National Human Genome Research Institute; Estados Unidos Fil: Jain, M.. National Human Genome Research Institute; Estados Unidos Fil: Acosta, M. T.. National Human Genome Research Institute; Estados Unidos Fil: Shively, S.. National Human Genome Research Institute; Estados Unidos. National Institute Of Neurological Disorders And Stroke; Estados Unidos Fil: Stanescu, H.. National Human Genome Research Institute; Estados Unidos Fil: Wallis, D.. National Human Genome Research Institute; Estados Unidos Fil: Domene, Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. National Human Genome Research Institute; Estados Unidos Fil: Vélez, J .I.. National Human Genome Research Institute; Estados Unidos Fil: Karkera, J. D.. National Human Genome Research Institute; Estados Unidos Fil: Balog, J.. National Human Genome Research Institute; Estados Unidos Fil: Berg, K.. National Human Genome Research Institute; Estados Unidos Fil: Kleta, R.. National Human Genome Research Institute; Estados Unidos Fil: Gahl, W. A.. National Human Genome Research Institute; Estados Unidos Fil: Roessler, E.. National Human Genome Research Institute; Estados Unidos Fil: Long, R.. National Human Genome Research Institute; Estados Unidos Fil: Lie, J.. National Institute Of Neurological Disorders And Stroke; Estados Unidos Fil: Pineda, D.. Universidad de Antioquia; Colombia Fil: Londoño, A. C.. Universidad de Antioquia; Colombia Fil: Palacio, J. D.. Universidad de Antioquia; Colombia Fil: Arbelaez, A.. Universidad de Antioquia; Colombia Fil: Lopera, F.. Universidad de Antioquia; Colombia Fil: Elia, J.. The Children's Hospital Of Philadelphia; Estados Unidos Fil: Hakonarson, H.. The Children's Hospital Of Philadelphia; Estados Unidos Fil: Johansson, S.. University Of Bergen; Noruega Fil: Knappskog, P. M.. University Of Bergen; Noruega Fil: Haavik, J.. University Of Bergen; Noruega Fil: Ribases, M.. Hospital Universitari Vall D'hebron; España Fil: Cormand, B.. Universidad de Barcelona; España Fil: Bayes, M.. Universidad de Barcelona; España Fil: Casas, M.. Universitat Autònoma de Barcelona; España. Hospital Universitari Vall D'hebron; España Fil: Ramos Quiroga, J. A.. Universitat Autònoma de Barcelona; España. Hospital Universitari Vall D'hebron; España Fil: Hervas, A.. Hospital Mutua de Terrassa; España Fil: Maher, B. S.. Virginia Institute For Psychiatric And Behavioral Genetics; Estados Unidos Fil: Faraone, S. V.. State University Of New York Upstate Medical University; Estados Unidos Fil: Seitz, C.. Saarland University Hospital; Alemania Fil: Freitag, C. M.. Saarland University Hospital; Alemania Fil: Palmason, H.. University of Trier; Alemania Fil: Meyer, J.. University of Trier; Alemania Fil: Romanos, M.. Universität Würzburg; Alemania Fil: Walitza, S.. Universität Würzburg; Alemania Fil: Hemminger, U.. Universität Würzburg; Alemania Fil: Warnke, A.. Universität Würzburg; Alemania Fil: Romanos, J.. Universität Würzburg; Alemania Fil: Renner, T.. Universität Würzburg; Alemania Fil: Jacob, C.. Universität Würzburg; Alemania Fil: Lesch, K. P.. Universität Würzburg; Alemania Fil: Swanson, J.. University of California at Irvine; Estados Unidos Fil: Vortmeyer, A.. National Human Genome Research Institute; Estados Unidos Fil: Bailey Wilson, J. E.. National Human Genome Research Institute; Estados Unidos Fil: Castellanos, F. X.. University of New York; Estados Unidos Fil: Muenke, M.. National Human Genome Research Institute; Estados Unidos
Databáze: OpenAIRE
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