title: Case-control and within-family tests for an association between conduct disorder and 5HTTLPR.
abstract: Several lines of research have suggested that serotonin dysfunction is associated with aggression, impulsivity, and antisocial behavior. A functional polymorphism in the promoter region (s, short and l, long allele variant) of the serotonin transporter gene (SLC6A4) that results in decreased transcription of the serotonin transporter gene has been linked with such serotonin dysfunction. To test for an association between 5HTTLPR genotype and conduct disorder diagnosis/aggression. Analysis for association between 5HTTLPR and conduct disorder/aggression using a case-control design and the transmission disequilibrium test. Conduct-disordered adolescents, who were drawn from admissions to a program that treats adolescents with serious substance and behavior problems, and conduct-disordered siblings of these patients (n, 297) were compared with non-conduct-disordered control adolescents and non-conduct-disordered siblings of these controls (n, 93). Second, using patient families where parental DNA was available, transmission disequilibrium tests were conducted for two phenotypes: (1) conduct disorder (74 trios), and (2) conduct disorder with at least one aggressive symptom (57 trios). Case-control analyses suggested a strong association between the ss genotype and conduct disorder (chi2(2) = 14.3; P < 0.01). Within-family analyses for conduct disorder with at least one aggressive symptom significantly favored greater transmission of the s-allele to affected offspring (chi(tdt)(2) = 4.13; P = 0.04); for conduct disorder, without aggressive symptoms, however, results were non-significant (chi(tdt)(2) = 1.61; P = 0.20). These data suggest that the s-allele may confer some risk for aggressive behavior or may be in linkage disequilibrium with such an allele.
authors.affiliation: Division of Substance Dependence, Department of Psychiatry, University of Colorado School of Medicine, Denver, CO, USA. joseph.sakai@uchsc.ed
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Sakai
authors.forename: Susan E
authors.initials: SE
authors.lastname: Young
authors.forename: Michael C
authors.initials: MC
authors.lastname: Stallings
authors.forename: David
authors.initials: D
authors.lastname: Timberlake
authors.forename: Andrew
authors.initials: A
authors.lastname: Smolen
authors.forename: Gary L
authors.initials: GL
authors.lastname: Stetler
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Crowley
mesh_terms: D000293:Adolescent; D000374:Aggression; D016022:Case-Control Studies; D019955:Conduct Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins