ADGRL3 (LPHN3) variants predict substance use disorder

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attentiondeficit/ hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and pred...

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Autores:
Arcos-Burgos, Mauricio
Vélez, Jorge I.
Martinez, Ariel F.
Ribasés, Marta
Ramos-Quiroga, Josep A.
Sánchez-Mora, Cristina
Richarte, Vanesa
Roncero, Carlos
Cormand, Bru
Fernández-Castillo, Noelia
Casas, Miguel
Lopera, Francisco
Pineda, David A.
Palacio, Juan D.
Acosta-López, Johan E.
Cervantes-Henriquez, Martha L.
Sánchez-Rojas, Manuel G.
Puentes-Rozo, Pedro J.
Molina, Brooke S. G.
MTA Cooperative Group
Boden, Margaret T.
Wallis, Deeann
Lidbury, Brett
Newman, Saul
Easteal, Simon
Swanson, James
Patel, Hardip
Volkow, Nora
Acosta, Maria T.
Castellanos, Francisco X.
de Leon, Jose
Mastronardi, Claudio A.
Muenke, Maximilian
Tipo de recurso:
Fecha de publicación:
2019
Institución:
Universidad Simón Bolívar
Repositorio:
Repositorio Digital USB
Idioma:
eng
OAI Identifier:
oai:bonga.unisimon.edu.co:20.500.12442/2555
Acceso en línea:
http://hdl.handle.net/20.500.12442/2555
Palabra clave:
Attention-deficit hyperactivity disorder (ADHD)
Conduct disorder
Brain damage
Rights
License
Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional
Description
Summary:Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attentiondeficit/ hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD.