Case-control and within-family tests for association between 5HTTLPR and conduct problems in a longitudinal adolescent sample.
BACKGROUND
Several recent studies have reported an association between the serotonin transporter 5HTTLPR (s-allele) and aggression; however, non-replications have also been reported. Inconsistencies may be explained by gene-environment interactions. Using a large general population sample, we sought to test for an association between 5HTTLPR and conduct problems, and to explore for a possible 5HTTLPR by maltreatment interaction.


METHODS
Using Caucasian adolescents from the genetic-pairs sample of the National Longitudinal Study of Adolescent Health (n=1,736), we tested for an association between 5HTTLPR and both a categorical and, separately, a continuous measure of conduct problems using regression analyses while controlling for sex, family effects, and age. We then tested for an association between 5HTTLPR and conduct problems using the within-family test Quantitative Transmission Disequilibrium Test. Analyses were repeated for a measure of adolescence-limited delinquency.


RESULTS
Results did not support an association between 5HTTLPR and conduct problems or delinquency. The Quantitative Transmission Disequilibrium Test analyses, which account for population stratification, were nonsignificant (F=0.17; P=0.68); introducing maltreatment as a covariate into the model did not affect this association (F=0.17; P=0.68). No association was seen between 5HTTLPR and a measure of adolescence-limited delinquency (F=0.54; P=0.46).


CONCLUSIONS
Using two methods in a large general population sample we did not find a significant association between 5HTTLPR and conduct problems. A gene by maltreatment interaction was not supported.
Sakai
Joseph T
JT
Division of Substance Dependence, Department of Psychiatry, University of Colorado School of Medicine, Denver CO 80262, USA. joseph.sakai@uchsc.edu
Lessem
Jeff M
JM
Haberstick
Brett C
BC
Hopfer
Christian J
CJ
Smolen
Andrew
A
Ehringer
Marissa A
MA
Timberlake
David
D
Hewitt
John K
JK
D000293:Adolescent; D000294:Adolescent Behavior; D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005190:Family; D006801:Humans; D007604:Juvenile Delinquency / Q000706:statistics & numerical data; D008137:Longitudinal Studies; D001523:Mental Disorders / Q000235:genetics*; D009061:Mouth Mucosa; D010641:Phenotype; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D035781:Siblings; D014158:Transcription, Genetic; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D044465:White People
D050486:Serotonin Plasma Membrane Transport Proteins; D004247:DNA