Skip navigation
Skip navigation

ADGRL3 (LPHN3) variants predict substance use disorder

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; 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

Description

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...[Show more]

dc.contributor.authorArcos-Burgos, Mauricio
dc.contributor.authorVélez, Jorge I
dc.contributor.authorMartinez, Ariel F
dc.contributor.authorRibasés, Marta
dc.contributor.authorRamos-Quiroga, Josep A
dc.contributor.authorSánchez-Mora, Cristina
dc.contributor.authorRicharte, Vanesa
dc.contributor.authorRoncero, Carlos
dc.contributor.authorCormand, Bru
dc.contributor.authorFernández-Castillo, Noelia
dc.contributor.authorCasas, Miguel
dc.contributor.authorLopera, Francisco
dc.contributor.authorPineda, David A
dc.contributor.authorPalacio, Juan D
dc.contributor.authorAcosta-López, Johan E
dc.contributor.authorCervantes-Henriquez, Martha L
dc.contributor.authorSánchez-Rojas, Manuel G
dc.contributor.authorPuentes-Rozo, Pedro J
dc.contributor.authorMolina, Brooke S G
dc.contributor.authorBoden, Margaret T
dc.contributor.authorWallis, Deeann
dc.contributor.authorLidbury, Brett
dc.contributor.authorNewman, Saul
dc.contributor.authorEasteal, Simon
dc.contributor.authorSwanson, James
dc.contributor.authorPatel, Hardip
dc.contributor.authorVolkow, Nora
dc.contributor.authorAcosta, Maria T
dc.contributor.authorCastellanos, Francisco X
dc.contributor.authorde Leon, Jose
dc.contributor.authorMastronardi, Claudio A
dc.contributor.authorMuenke, Maximilian
dc.date.accessioned2019-03-12T00:06:26Z
dc.date.available2019-03-12T00:06:26Z
dc.identifier.urihttp://hdl.handle.net/1885/157063
dc.description.abstractGenetic 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.
dc.description.sponsorshipThis study was supported by the National Human Genome Research Institute intramural funds (to M.M.) for the ascertainment of patients from the Paisa population. The Kentucky sample was ascertained using funds from the Eli Lilly Research Foundation (to J.d.L.), a National Alliance for Research on Schizophrenia and Depression (NARSAD) Independent Award (to J.d.L.), University of Kentucky internal funding (to J.d.L.), and Roche Molecular Systems, Inc., who provided free genotyping and laboratory supplies (to J.d.L.). J.I.V. is partially supported by research grant FOFICO 32101-511035-PE0031 from Universidad del Norte, Barranquilla, Colombia. The Multimodal Treatment Study of Children with ADHD (MTA) was a National Institute of Mental Health (NIMH) cooperative agreement randomized clinical trial, continued under an NIMH contract as a follow-up study and finally under a National Institute on Drug Abuse (NIDA) contract followed by a data analysis grant (DA039881). The Spanish sample was recruited, assessed and genotyped using funds from the Instituto de Salud Carlos III, Spain (PI12/01139, PI14/01700, PI15/01789, PI16/ 01505), and co-financed by the European Regional Development Fund (ERDF); Agència de Gestió d’Ajuts Universitaris i de Recerca-AGAUR, Generalitat de Catalunya (2014SGR1357, 2014SGR0932); Departament de Salut, Generalitat de Catalunya; Ministerio de Economía, Industria y Competitividad, Spain (SAF2015-68341-R); the European College of Neuropsychopharmacology (ECNP network: ‘ADHD across the lifespan’) and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. This project has also received funding from the European Union’s Horizon 2020 research and innovation programme (CoCA under grant agreement 667302). C.S.-M. is recipient of a Sara Borrell contract from the Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad, Spain (CD15/00199). M.R. is a recipient of a Miguel de Servet contract from the Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad, Spain (CP09/00119 and CPII15/00023). N.F.-C. was supported by a contract of the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER).
dc.format15 pages
dc.format.mimetypeapplication/pdf
dc.language.isoen_AU
dc.publisherSpringer Nature
dc.rights© The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.sourceTranslational psychiatry
dc.subjectattention-deficit/hyperactivity disorder (ADHD)
dc.subjectoppositional defiant disorder
dc.subjectconduct disorder
dc.subjectsubstance use disorder (SUD)
dc.subjectADGRL3 (LPHN3) gene
dc.titleADGRL3 (LPHN3) variants predict substance use disorder
dc.typeJournal article
local.identifier.citationvolume9
dcterms.dateAccepted2019-01-02
dc.date.issued2019-01-29
local.identifier.ariespublicationU1070655xPUB127
local.publisher.urlhttps://www.nature.com/
local.type.statusPublished Version
local.contributor.affiliationLidbury, Brett, National Centre for Epidemiology & Population Health, CHM Research School of Population Health, The Australian National University
local.contributor.affiliationNewman, Saul, National Centre for Epidemiology & Population Health, CHM Research School of Population Health, The Australian National University
local.contributor.affiliationEasteal, Simon, National Centre for Epidemiology & Population Health, CHM Research School of Population Health, The Australian National University
local.contributor.affiliationPatel, Hardip, Genome Sciences, CHM John Curtin School of Medical Research, The Australian National University
local.identifier.essn2158-3188
local.bibliographicCitation.issue1
local.bibliographicCitation.startpage42
local.identifier.doi10.1038/s41398-019-0396-7
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

Download

File Description SizeFormat Image
01 Arcos Burgos M et al ADGRL3 (LPHN3) variants 2019.pdf2.53 MBAdobe PDFThumbnail


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  19 May 2020/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator