ADGRL3 (LPHN3) variants predict substance use disorder

被引：32

作者：

Arcos-Burgos, Mauricio ^{[1
,2
,3
]}

Velez, Jorge, I ^{[1
,4
]}

Martinez, Ariel F. ^{[1
]}

Ribases, Marta ^{[5
,6
,7
]}

Ramos-Quiroga, Josep A. ^{[5
,6
,7
,8
]}

Sanchez-Mora, Cristina ^{[5
,6
,7
]}

Richarte, Vanesa ^{[6
,7
,8
]}

Roncero, Carlos ^{[6
,7
,8
,9
]}

Cormand, Bru ^{[10
,11
,12
,13
]}

Fernandez-Castillo, Noelia ^{[10
,11
,12
,13
]}

Casas, Miguel ^{[5
,6
,7
,8
]}

Lopera, Francisco ^{[14
]}

Pineda, David A. ^{[14
]}

Palacio, Juan D. ^{[14
]}

Acosta-Lopez, Johan E. ^{[15
]}

Cervantes-Henriquez, Martha L. ^{[4
,15
]}

Sanchez-Rojas, Manuel G. ^{[15
]}

Puentes-Rozo, Pedro J. ^{[15
,16
]}

Molina, Brooke S. G. ^{[17
,18
]}

Boden, Margaret T. ^{[19
]}

Wallis, Deeann ^{[20
]}

Lidbury, Brett ^{[21
]}

Newman, Saul ^{[21
]}

Easteal, Simon ^{[21
]}

Swanson, James ^{[22
,23
,40
]}

Patel, Hardip ^{[24
]}

Volkow, Nora ^{[25
]}

Acosta, Maria T. ^{[1
]}

Castellanos, Francisco X. ^{[26
,27
]}

de Leon, Jose ^{[19
]}

Mastronardi, Claudio A. ^{[2
,28
]}

Muenke, Maximilian ^{[1
]}

Vitiello, Benedetto ^{[29
]}

Severe, Joanne B. ^{[30
]}

Jensen, Peter S. ^{[31
]}

Arnold, L. Eugene ^{[32
]}

Hoagwood, Kimberly ^{[33
]}

Richters, John ^{[34
]}

Vereen, Donald ^{[35
]}

Hinshaw, Stephen P. ^{[36
]}

Elliott, Glen R. ^{[37
]}

Wells, Karen C. ^{[38
]}

Epstein, Jeffery N. ^{[39
]}

Murray, Desiree W.

Conners, C. Keith

March, John

Wigal, Timothy

Cantwell, Dennis P.

Abikoff, Howard B. ^{[33
]}

Hechtman, Lily ^{[41
]}

机构：

[1] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA

[2] Fdn Univ Sanitas, INPAC Res Grp, Bogota, Colombia

[3] Univ Antioquia, Fac Med, IIM, Medellin, Colombia

[4] Univ Norte, Barranquilla, Colombia

[5] Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Grp Psychiat Mental Hlth & Addict, Psychiat Genet Unit, Barcelona, Spain

[6] Hosp Universitari Vail dHebron, Dept Psychiat, Barcelona, Spain

[7] Biomed Network Res Ctr Mental Hlth CIBERSAM, Barcelona, Spain

[8] Univ Autonoma Barcelona, Dept Psychiat & Legal Med, Barcelona, Spain

[9] Hosp Univ Vall dHebron, Dept Psychiat, Addict & Dual Diag Unit, Publ Hlth Agcy, Barcelona, Spain

[10] Univ Barcelona, Dept Genet Microbiol & Stat, Barcelona, Cat, Spain

[11] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain

[12] IBUB, Barcelona, Cat, Spain

[13] IRSJD, Esplugues, Cat, Spain

[14] Univ Antioquia, Neurosci Res Grp, Medellin, Colombia

[15] Univ Simon Bolivar, Grp Neurociencias Caribe, Unidad Neurociencias Cognit, Barranquilla, Colombia

[16] Univ Atlantico, Grp Neurociencias Caribe, Barranquilla, Colombia

[17] Univ Pittsburg, Dept Psychiat, Pittsburgh, PA USA

[18] Univ Pittsburg, Dept Psychol, Pittsburgh, PA USA

[19] Univ Kentucky, Mental Hlth Res Ctr, Eastern State Hosp, Lexington, KY USA

[20] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA

[21] Australian Natl Univ, Natl Ctr Indigenous Genom, Genome Biol Dept, John Curtin Sch Med Res,ANU Coll Med Biol & Envir, Canberra, ACT, Australia

[22] Florida Int Univ, Dept Psychiat, Miami, FL 33199 USA

[23] Univ Calif Irvine, Child Dev Ctr, Irvine, CA USA

[24] Australian Natl Univ, Genome Discovery Unit, Genome Biol Dept, John Curtin Sch Med Res,ANU Coll Med Biol & Envir, Canberra, ACT, Australia

[25] NIDA, Off Director, NIH, Rockville, MD USA

[26] NYU Langone, Dept Child & Adolescent Psychiat, Hassenfeld Childrens Hosp, New York, NY USA

[27] Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA

[28] Univ Rosario, Sch Med & Hlth Sci, Inst Translat Med, Ctr Res Genet & Genom, Bogota, Colombia

[29] Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD USA

[30] Div Serv & Intervent Res, Clin Trials Operat & Biostat Unit, Bethesda, MD USA

[31] REACH Inst, New York, NY USA

[32] Ohio State Univ, Columbus, OH 43210 USA

[33] NYU, Sch Med, New York, NY 10003 USA

[34] NINR, Bethesda, MD 20892 USA

[35] NIDA, Bethesda, MD 20892 USA

[36] Univ Calif Berkeley, Berkeley, CA 94720 USA

[37] Univ Calif San Francisco, San Francisco, CA 94143 USA

[38] Duke Univ, Durham, NC 27706 USA

[39] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

[40] Univ Calif Irvine, Irvine, CA USA

[41] McGill Univ, Montreal Childrens Hosp, Montreal, PQ, Canada

[42] Columbia Univ, New York State Psychiat Inst, Mt Sinai Med Ctr, New York, NY 10027 USA

[43] Univ Pittsburgh, Mt Sinai Sch Med, Pittsburgh, PA 15260 USA

[44] Univ Vermont, Burlington, VT 05405 USA

[45] Florida Int Univ, Miami, FL 33199 USA

[46] Univ Illinois, Chicago, IL USA

[47] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[48] Stanford Univ, Stanford, CA 94305 USA

[49] US DOE, Off Special Educ Programs, Washington, DC 20585 USA

[50] US Dept Justice, Off Juvenile Justice & Delinquency Prevent, Washington, DC 20530 USA

来源：

TRANSLATIONAL PSYCHIATRY | 2019年 / 9卷 / 1期

基金：

欧盟地平线“2020”;

关键词：

ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; COMMON GENETIC-VARIANTS; FOLLOW-UP; DIAGNOSTIC INTERVIEW; MULTIMODAL TREATMENT; ALCOHOL DEPENDENCE; CONDUCT DISORDER; ADHD MEDICATION; ADULT OUTCOMES;

D O I：

10.1038/s41398-019-0396-7

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

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.

引用

页数：15

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