ADGRL3 (LPHN3) variants predict substance use disorder

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/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. © 2019, The Author(s).

• Fecha de publicación: 2019
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/23388
• Acceso en línea: https://doi.org/10.1038/s41398-019-0396-7; https://repository.urosario.edu.co/handle/10336/23388
• Palabra clave: Adhesion g protein coupled receptor l3; Amphetamine derivative; Barbituric acid derivative; Cocaine; G protein coupled receptor; Genomic dna; Opiate; Psychedelic agent; Sedative agent; Unclassified drug; G protein coupled receptor; Receptor; Adhesion g protein coupled receptor l3 gene; Adolescent; Adult; Alcoholism; Article; Attention deficit disorder; Cannabis addiction; Child; Clinical assessment; Cohort analysis; Comorbidity; Controlled study; Demography; Disease predisposition; Family; Female; Gene; Gene locus; Genetic association; Genetic epidemiology; Genetic model; Genetic risk; Genetic variability; Human; Longitudinal study; Major clinical study; Male; Pharmacogenetic testing; Population based case control study; Prediction; Randomized controlled trial; Retrospective study; Tobacco dependence; Case control study; Drug dependence; Genetic predisposition; Genetics; Risk factor; Single nucleotide polymorphism; Young adult; Adult; Case-control studies; Female; Genetic predisposition to disease; Humans; Longitudinal studies; Male; Risk factors; Substance-related disorders; Young adult; single nucleotide; g-protein-coupled; human; peptide; Lphn3 protein; Polymorphism; Receptors; Receptors
• License: Abierto (Texto Completo)