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
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License
Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional
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dc.title.eng.fl_str_mv ADGRL3 (LPHN3) variants predict substance use disorder
title ADGRL3 (LPHN3) variants predict substance use disorder
spellingShingle ADGRL3 (LPHN3) variants predict substance use disorder
Attention-deficit hyperactivity disorder (ADHD)
Conduct disorder
Brain damage
title_short ADGRL3 (LPHN3) variants predict substance use disorder
title_full ADGRL3 (LPHN3) variants predict substance use disorder
title_fullStr ADGRL3 (LPHN3) variants predict substance use disorder
title_full_unstemmed ADGRL3 (LPHN3) variants predict substance use disorder
title_sort ADGRL3 (LPHN3) variants predict substance use disorder
dc.creator.fl_str_mv 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
dc.contributor.author.none.fl_str_mv 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
dc.subject.eng.fl_str_mv Attention-deficit hyperactivity disorder (ADHD)
Conduct disorder
Brain damage
topic Attention-deficit hyperactivity disorder (ADHD)
Conduct disorder
Brain damage
description 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.
publishDate 2019
dc.date.accessioned.none.fl_str_mv 2019-02-04T21:20:25Z
dc.date.available.none.fl_str_mv 2019-02-04T21:20:25Z
dc.date.issued.none.fl_str_mv 2019-01
dc.type.eng.fl_str_mv article
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.identifier.issn.none.fl_str_mv 21583188
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12442/2555
identifier_str_mv 21583188
url http://hdl.handle.net/20.500.12442/2555
dc.language.iso.eng.fl_str_mv eng
language eng
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dc.rights.license.spa.fl_str_mv Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional
rights_invalid_str_mv Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional
http://purl.org/coar/access_right/c_abf2
dc.publisher.eng.fl_str_mv Nature Research
dc.source.eng.fl_str_mv Translational Psychiatry
institution Universidad Simón Bolívar
dc.source.uri.eng.fl_str_mv https://www.nature.com/articles/s41398-019-0396-7
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spelling Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacionalhttp://purl.org/coar/access_right/c_abf2Arcos-Burgos, Mauriciob0eeb625-a6f6-4508-8925-309b5f765a14-1Vélez, Jorge I.83044e45-79cc-4eec-a9cc-72bf4514e76b-1Martinez, Ariel F.58157e12-a4c9-47bb-b7ee-ecaafc3d7429-1Ribasés, Martaa440160f-4b51-4a7a-a882-543197243aef-1Ramos-Quiroga, Josep A.748706d9-c800-488c-9079-f97ab4374b22-1Sánchez-Mora, Cristina536116a7-7c7c-4d49-b0fd-3788b954ea3b-1Richarte, Vanesa594dd018-55c7-4526-a99d-3423577f3034-1Roncero, Carlos6bc177c8-290d-4075-b645-acc1a06e03be-1Cormand, Bru1960535e-12b7-44a7-91cf-0b3224839e51-1Fernández-Castillo, Noeliad72b2a39-703e-4274-ad3f-1b605829d23f-1Casas, Miguel7e5c74b3-c6e7-4076-ba79-b393800b02f1-1Lopera, Francisco4a86ad59-fb7c-4ff9-8b91-2eec6406d886-1Pineda, David A.7fa7af6f-d0cb-4f00-b3bf-d0b4188e1ffa-1Palacio, Juan D.15bc4075-dd4c-4e26-b64d-f1444a402d0b-1Acosta-López, Johan E.b7a16ff4-ce8a-419c-a6ba-597013d207ed-1Cervantes-Henriquez, Martha L.f508e4e4-ef3d-4178-9673-41707c950511-1Sánchez-Rojas, Manuel G.56e48e09-40b4-4114-802e-84a20ae146ae-1Puentes-Rozo, Pedro J.f5776586-b6b2-4086-8bed-3e4972516196-1Molina, Brooke S. G.4d2b8c20-0e96-4ce4-b511-0956f1521ffd-1MTA Cooperative Groupf8c21537-54c8-424d-b8e1-2a001c1e13da-1Boden, Margaret T.f02ba835-55bb-43b0-bd24-c8f7027993c2-1Wallis, Deeannc10ca69d-2046-455f-9ab1-046451f4059b-1Lidbury, Brettc1cc5988-6ef9-4d8f-a2a4-3f4c01370cfc-1Newman, Saule41c3749-fd88-4927-bfac-ec80e0a387a4-1Easteal, Simon8b0a5f8e-583d-4bc3-91d3-012b7ae80811-1Swanson, James5184a6ea-ab1d-4d76-9b61-2bf825d36bf2-1Patel, Hardip107803ed-0aea-45f7-8ac6-0d88630da8d5-1Volkow, Norae126e3b3-718c-40a8-a206-8edc251a1bad-1Acosta, Maria T.89d3a9bf-3c56-41ab-ae0b-66b5ed6c021d-1Castellanos, Francisco X.9266ad0a-b6a2-4724-a754-f4575026067d-1de Leon, Jose6eb8d89e-260b-4c23-b2d7-a332b93288d3-1Mastronardi, Claudio A.55aa2248-59ef-49ea-9101-21682e3932a0-1Muenke, Maximilianf0dbb77f-ed4b-4515-ad4e-6ec17a1e90e3-12019-02-04T21:20:25Z2019-02-04T21:20:25Z2019-0121583188http://hdl.handle.net/20.500.12442/2555Genetic 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.engNature ResearchTranslational Psychiatryhttps://www.nature.com/articles/s41398-019-0396-7Attention-deficit hyperactivity disorder (ADHD)Conduct disorderBrain damageADGRL3 (LPHN3) variants predict substance use disorderarticlehttp://purl.org/coar/resource_type/c_6501Whiteford, H. A., Ferrari, A. J., Degenhardt, L., Feigin, V. & Vos, T. The global burden of mental, neurological and substance use disorders: an analysis from the Global Burden of Disease Study 2010. PLoS ONE 10, e0116820 (2015).Heslin K. C., Elixhauser A., Steiner C. A. Hospitalizations Involving Mental and Substance Use Disorders Among Adults, 2012: Statistical Brief #191 Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. (Agency for Healthcare Research and Quality, Rockville, MD, 2010).Prom-Wormley, E. C., Ebejer, J., Dick, D. M. & Bowers, M. S. The genetic epidemiology of substance use disorder: a review. Drug Alcohol. Depend. 180, 241–259 (2017).Centers for Disease C, Prevention. Increasing prevalence of parent-reported attention-deficit/hyperactivity disorder among children—United States, 2003 and 2007. Mmwr. Morb. Mortal. Wkly. Rep. 59, 1439–1443 (2010).Visser, S. N. et al. Trends in the parent-report of health care provider-diagnosed and medicated attention-deficit/hyperactivity disorder: United States, 2003–2011. J. Am. Acad. Child Adolesc. Psychiatry 53, 34–46 e2 (2014).Palacio, J. D. et al. Attention-deficit/hyperactivity disorder and comorbidities in 18 Paisa Colombian multigenerational families. J. Am. Acad. Child Adolesc. Psychiatry 43, 1506–1515 (2004).Sibley, M. H. et al. The delinquency outcomes of boys with ADHD with and without comorbidity. J. Abnorm. Child Psychol. 39, 21–32 (2011).Jain, M. et al. Attention-deficit/hyperactivity disorder and comorbid disruptive behavior disorders: evidence of pleiotropy and new susceptibility loci. Biol. Psychiatry 61, 1329–1339 (2007).Kuperman, S. et al. Developmental sequence from disruptive behavior diagnosis to adolescent alcohol dependence. Am. J. Psychiatry 158, 2022–2026 (2001).Molina, B. S. et al. Adolescent substance use in the multimodal treatment study of attention-deficit/hyperactivity disorder (ADHD) (MTA) as a function of childhood ADHD, random assignment to childhood treatments, and subsequent medication. J. Am. Acad. Child Adolesc. Psychiatry 52, 250–263 (2013).Molina, B. S. G. & Pelham, W. E. Childhood predictors of adolescent substance use in a longitudinal study of children with ADHD. J. Abnorm. Psychol. 112, 497–507 (2003).Biederman, J. et al. Psychoactive substance use disorders in adults with attention-deficit hyperactivity Disorder (ADHD)—effects of ADHD and psychiatric comorbidity. Am. J. Psychiatry 152, 1652–1658 (1995).Nogueira, M. et al. Early-age clinical and developmental features associated to substance use disorders in attention-deficit/hyperactivity disorder in adults. Compr. Psychiatry 55, 639–649 (2014).DeMilio, L. Psychiatric syndromes in adolescent substance abusers. Am. J. Psychiatry 146, 1212–1214 (1989).Horner, B. R. & Scheibe, K. E. Prevalence and implications of attention-deficit hyperactivity disorder among adolescents in treatment for substance abuse. J. Am. Acad. Child Adolesc. Psychiatry 36, 30–36 (1997).Ercan, E. S., Coskunol, H., Varan, A. & Toksoz, K. Childhood attention deficit/ hyperactivity disorder and alcohol dependence: a 1-year follow-up. Alcohol. Alcohol. 38, 352–356 (2003).White, A. M. et al. Predictors of relapse during treatment and treatment completion among marijuana-dependent adolescents in an intensive outpatient substance abuse program. Subst. Abus. 25, 53–59 (2004).Arcos-Burgos, M., Velez, J. I., Solomon, B. D. & Muenke, M. A common genetic network underlies substance use disorders and disruptive or externalizing disorders. Hum. Genet. 131, 917–929 (2012).Gorwood, P. et al. Genetics of dopamine receptors and drug addiction. Hum. Genet. 131, 803–822 (2012).Hart, A. B. et al. Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13). PLoS ONE 7, e42646 (2012).Li, M. D. & Burmeister, M. New insights into the genetics of addiction. Nat. Rev. Genet. 10, 225–231 (2009).Acosta, M. T. et al. Latent class subtyping of attention-deficit/hyperactivity disorder and comorbid conditions. J. Am. Acad. Child Adolesc. Psychiatry 47, 797–807 (2008).Arcos-Burgos, M. et al. Attention-deficit/hyperactivity disorder (ADHD): feasibility of linkage analysis in a genetic isolate using extended and multigenerational pedigrees. Clin. Genet. 61, 335–343 (2002).Acosta, M. T. et al. A two-locus genetic interaction between LPHN3 and 11q predicts ADHD severity and long-term outcome. Transl. Psychiatry 1, e17 (2011).Arcos-Burgos, M. et al. Attention-deficit/hyperactivity disorder in a population isolate: linkage to loci at 4q13.2, 5q33.3, 11q22, and 17p11. Am. J. Hum. Genet. 75, 998–1014 (2004).Acosta, M. T. et al. ADGRL3 (LPHN3) variants are associated with a refined phenotype of ADHD in the MTA study. Mol. Genet. Genom. Med. 4, 540–547 (2016).Bruxel, E. M. et al. LPHN3 and attention-deficit/hyperactivity disorder: a susceptibility and pharmacogenetic study. Genes. Brain. Behav. 14, 419–427 (2015).Hwang, I. W., Lim, M. H., Kwon, H. J. & Jin, H. J. Association of LPHN3rs6551665 A/G polymorphism with attention deficit and hyperactivity disorder in Korean children. Gene 566, 68–73 (2015).Jain, M. et al. A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD. Mol. Psychiatry 17, 741–747 (2012).Arcos-Burgos, M. et al. A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Mol. Psychiatry 15, 1053–1066 (2010).Labbe, A. et al. Refining psychiatric phenotypes for response to treatment: contribution of LPHN3 in ADHD. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 159B, 776–785 (2012).Ribases, M. et al. Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study. Genes. Brain. Behav. 10, 149–157 (2011).Song, J. et al. Association of SNAP-25, SLC6A2, and LPHN3 with OROS methylphenidate treatment response in attention-deficit/hyperactivity disorder. Clin. Neuropharmacol. 37, 136–141 (2014).Gomez-Sanchez, C. I. et al. Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children. Behav. Brain. Funct. 12, 2 (2016).Gomez-Sanchez, C. I. et al. Attention deficit hyperactivity disorder: genetic association study in a cohort of Spanish children. Behav. Brain. Funct. 12, 2 (2016).Ramos-Quiroga, J. A. et al. Criterion and concurrent validity of Conners Adult ADHD Diagnostic Interview for DSM-IV (CAADID) Spanish version. Rev. Psiquiatr Salud Ment. 5, 229–235 (2012).Group, T. M. C. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal treatment study of children with ADHD. Arch. Gen. Psychiatry 56, 1073–1086 (1999).Jensen, P. S. et al. 3-year follow-up of the NIMH MTA study. J. Am. Acad. Child Adolesc. Psychiatry 46, 989–1002 (2007).Molina, B. S. et al. The MTA at 8 years: prospective follow-up of children treated for combined-type ADHD in a multisite study. J. Am. Acad. Child Adolesc. Psychiatry 48, 484–500 (2009).Hechtman, L. et al. Functional adult outcomes 16 years after childhood diagnosis of attention-deficit/hyperactivity disorder: MTA results. J. Am. Acad. Child Adolesc. Psychiatry 55, 945–52 e2 (2016).Swanson, J. M. et al. Young adult outcomes in the follow-up of the multimodal treatment study of attention-deficit/hyperactivity disorder: symptom persistence, source discrepancy, and height suppression. J. Child Psychol. Psychiatry 58, 663–678 (2017).Roy, A. et al. Childhood predictors of adult functional outcomes in the multimodal treatment study of attention-deficit/hyperactivity disorder (MTA). J. Am. Acad. Child Adolesc. Psychiatry 56, 687–95 e7 (2017).Molina, B. S. et al. Delinquent behavior and emerging substance use in the MTA at 36 months: prevalence, course, and treatment effects. J. Am. Acad. Child Adolesc. Psychiatry 46, 1028–1040 (2007).Johnson, C. et al. Pooled association genome scanning for alcohol dependence using 104,268 SNPs: validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 141B, 844–853 (2006).Uhl GR. Molecular genetics of substance abuse vulnerability: remarkable recent convergence of genome scan results. Ann. N. Y. Acad. Sci. 1025, 1–13 (2004).Shaffer, D., Fisher, P., Lucas, C. P., Dulcan, M. K. & Schwab-Stone, M. E. NIMH Diagnostic Interview Schedule for Children Version IV (NIMH DISC-IV): description, differences from previous versions, and reliability of some common diagnoses. J. Am. Acad. Child Adolesc. Psychiatry 39, 28–38 (2000).Robins L. N., Cottler L., Bucholz K., Compton W. The Diagnostic Interview Schedule for DSM-IV (DIS-IV). (Washington University School of Medicine, St. Louis, MO, 2000).de Leon, J., Susce, M. T., Diaz, F. J., Rendon, D. M. & Velasquez, D. M. Variables associated with alcohol, drug, and daily smoking cessation in patients with severe mental illnesses. J. Clin. Psychiatry 66, 1447–1455 (2005).Drake, R. E., Mchugo, G. J. & Biesanz, J. C. The test-retest reliability of standardized instruments among homeless persons with substance use disorders. J. Stud. Alcohol. 56, 161–167 (1995).Drake, R. E., Rosenberg, S. D. & Mueser, K. T. Assessing substance use disorder in persons with severe mental illness. New Dir. Ment. Health Serv. 1996, 3–17 (1996).de Leon, J., Armstrong, S. C. & Cozza, K. L. Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 2C19. Psychosomatics 47, 75–85 (2006).Arcos-Burgos, M. & Muenke, M. Toward a better understanding of ADHD: LPHN3 gene variants and the susceptibility to develop ADHD. Atten. Defic. Hyperact Disord. 2, 139–147 (2010).Wong, M. L., Dong, C., Andreev, V., Arcos-Burgos, M. & Licinio, J. Prediction of susceptibility to major depression by a model of interactions of multiple functional genetic variants and environmental factors. Mol. Psychiatry 17, 624–633 (2012).Rao, D. C. CAT scans, PET scans, and genomic scans. Genet. Epidemiol. 15, 1–18 (1998).Ryzin, J. V., Breiman, L., Friedman, J. H., Olshen, R. A. & Stone, C. J. Classification and regression trees. J. Am. Stat. Assoc. 81, 253 (1986).Breiman L. Random Forests. In Machine Learning, Vol. 45.(ed. Schapire, R. E.) (Kluwer Academic Publishers, The Netherlands, 2001).Friedman J. H. Greedy Function Approximation: a Gradient Boosting Machine. (University of Stanford, Stanford, CA, 1999).Marjoram, P., Zubair, A. & Nuzhdin, S. V. Post-GWAS: where next? More samples, more SNPs or more biology? Hered. (Edinb.) 112, 79–88 (2014).Visscher, P. M., Brown, M. A., McCarthy, M. I. & Yang, J. Five years of GWAS discovery. Am. J. Hum. Genet. 90, 7–24 (2012).Melroy-Greif, W. E. et al. Examination of the involvement of cholinergicassociated genes in nicotine behaviors in European and African Americans. Nicotine. Tob. Res. 19, 417–425 (2017).Polimanti, R., Yang, C., Zhao, H. & Gelernter, J. Dissecting ancestry genomic background in substance dependence genome-wide association studies. Pharmacogenomics 16, 1487–1498 (2015).Bi, J., Gelernter, J., Sun, J. & Kranzler, H. R. Comparing the utility of homogeneous subtypes of cocaine use and related behaviors with DSM-IV cocaine dependence as traits for genetic association analysis. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 165B, 148–156 (2014).Palmer, R. H. et al. Examining the role of common genetic variants on alcohol, tobacco, cannabis and illicit drug dependence: genetics of vulnerability to drug dependence. Addiction 110, 530–537 (2015).Neale, B. M. & Sham, P. C. The future of association studies: gene-based analysis and replication. Am. J. Hum. Genet. 75, 353–362 (2004).Demontis, D. et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat. Genet. 51, 63–75 (2019).Stergiakouli, E. et al. Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD. Am. J. Psychiatry 169, 186–194 (2012).Poelmans, G., Pauls, D. L., Buitelaar, J. K. & Franke, B. Integrated genome-wide association study findings: identification of a neurodevelopmental network for attention deficit hyperactivity disorder. Am. J. Psychiatry 168, 365–377 (2011).Williams, N. M. et al. Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3. Am. J. Psychiatry 169, 195–204 (2012).Choudhry, Z. et al. LPHN3 and attention-deficit/hyperactivity disorder: interaction with maternal stress during pregnancy. J. Child Psychol. Psychiatry 53, 892–902 (2012).Martinez, A. F., Muenke, M. & Arcos-Burgos, M. From the black widow spider to human behavior: Latrophilins, a relatively unknown class of G protein-coupled receptors, are implicated in psychiatric disorders. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 156B, 1–10 (2011).Koob, G. F. & Volkow, N. D. Neurocircuitry of addiction. Neuropsychopharmacology 35, 217–238 (2010).Lange, M. et al. The ADHD-susceptibility genelphn3.1 modulates dopaminergic neuron formation and locomotor activity during zebrafish development. Mol. Psychiatry 17, 946–954 (2012).Wallis, D. et al. Initial characterization of mice null for Lphn3, a gene implicated in ADHD and addiction. Brain Res. 1463, 85–92 (2012).O'Sullivan, M. L. et al. FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development. Neuron 73, 903–910 (2012).Chassin L., Colder C. R., Hussong A., Sher K. J. Substance Use and Substance Use Disorders. (ed. Cicchetti, D.) Developmental Psychopathology, 2nd edn, Vol. 3. (John Wiley & Sons, Inc., Hoboken, NJ, 2016) pp 833-897.Brook, J. S., Balka, E. B., Zhang, C. & Brook, D. W. ADHD, conduct disorder, substance use disorder, and nonprescription stimulant use. J. Atten. Disord. 21, 776–782 (2017).Molina, B. S. & Pelham, W. E. Jr. Attention-deficit/hyperactivity disorder and risk of substance use disorder: developmental considerations, potential pathways, and opportunities for research. Annu. Rev. Clin. Psychol. 10, 607–639 (2014).Zulauf, C. A., Sprich, S. E., Safren, S. A. & Wilens, T. E. The complicated relationship between attention deficit/hyperactivity disorder and substance use disorders. Curr. Psychiatry Rep. 16, 436 (2014).Wilens, T. E. & Biederman, J. Alcohol, drugs, and attention-deficit/ hyperactivity disorder: a model for the study of addictions in youth. J. Psychopharmacol. 20, 580–588 (2006).Estevez-Lamorte, N. et al. Adult attention-deficit/hyperactivity disorder, risky substance use and substance use disorders: a follow-up study among young men. Eur. Arch. Psychiatry Clin. Neurosci. (2018). https://doi.org/10.1007/s00406- 018-0958-3.Chen, Q. et al. Common psychiatric and metabolic comorbidity of adult attention-deficit/hyperactivity disorder: a population-based cross-sectional study. PLoS ONE 13, e0204516 (2018).Quinn, P. D. et al. ADHD medication and substance-related problems. Am. J. Psychiatry 174, 877–885 (2017).Chang, Z. et al. Stimulant ADHD medication and risk for substance abuse. J. Child Psychol. Psychiatry 55, 878–885 (2014).Groenman, A. P. et al. Substance use disorders in adolescents with attention deficit hyperactivity disorder: a 4-year follow-up study. Addiction 108, 1503–1511 (2013).Flory, K. & Lynam, D. R. The relation between attention deficit hyperactivity disorder and substance abuse: what role does conduct disorder play? Clin. Child Fam. Psychol. Rev. 6, 1–16 (2003).Lee, S. S., Humphreys, K. L., Flory, K., Liu, R. & Glass, K. Prospective association of childhood attention-deficit/hyperactivity disorder (ADHD) and substance use and abuse/dependence: a meta-analytic review. Clin. Psychol. Rev. 31, 328–341 (2011).Valero, S. et al. Personality profile of adult ADHD: the alternative five factor model. Psychiatry Res. 198, 130–134 (2012).Khantzian, E. J. The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harv. Rev. Psychiatry 4, 231–244 (1997).Pedersen, S. L., Harty, S. C., Pelham, W. E., Gnagy, E. M. & Molina, B. S. G. Differential associations between alcohol expectancies and adolescent alcohol use as a function of childhood ADHD. J. Stud. Alcohol. 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