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

• Autores: Arcos Burgos, M.; Jain, M.; Acosta, M. T.; Shively, S.; Stanescu, H.; Wallis, D.; Domene, Sabina; Vélez, J .I.; Karkera, J. D.; Balog, J.; Berg, K.; Kleta, R.; Gahl, W. A.; Roessler, E.; Long, R.; Lie, J.; Pineda, D.; Londoño, A. C.; Palacio, J. D.; Arbelaez, A.; Lopera, F.; Elia, J.; Hakonarson, H.; Johansson, S.; Knappskog, P. M.; Haavik, J.; Ribases, M.; Cormand, B.; Bayes, M.; Casas, M.; Ramos Quiroga, J. A.; Hervas, A.; Maher, B. S.; Faraone, S. V.; Seitz, C.; Freitag, C. M.; Palmason, H.; Meyer, J.; Romanos, M.; Walitza, S.; Hemminger, U.; Warnke, A.; Romanos, J.; Renner, T.; Jacob, C.; Lesch, K. P.; Swanson, J.; Vortmeyer, A.; Bailey Wilson, J. E.; Castellanos, F. X.; Muenke, M.
• Año de publicación: 2010
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: ADHD; COMPLEX TRAIT; GENE; GENETICS; LATROPHILIN; LPHN3
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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