ADGRL3 (LPHN3) variants predict substance use disorder
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Fecha
2019-01
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
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Editor
Nature Research
Resumen
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.
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Palabras clave
Attention-deficit hyperactivity disorder (ADHD), Conduct disorder, Brain damage