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Using trajectory analyses to refine phenotype for genetic association: conduct problems and the serotonin transporter (5HTTLPR)

Sakai, Joseph T.a; Boardman, Jason D.b; Gelhorn, Heather L.d; Smolen, Andrewb; Corley, Robin P.b; Huizinga, Davidb; Menard, Scottb c; Hewitt, John K.b; Stallings, Michael C.b

doi: 10.1097/YPG.0b013e32833a20f1
Original Articles

Background: Conduct disorder is a serious, relatively common disorder of childhood and adolescence. Findings from genetic association studies searching for genetic determinants of the liability toward such behaviors have been inconsistent. One possible explanation for differential results is that most studies define phenotype from a single assessment; for many adolescents conduct problems decrease in severity over time, whereas for others such behaviors persist. Therefore, longitudinal datasets offer the opportunity to refine phenotype.

Methods: We used Caucasians that were first assessed during adolescence from the National Youth Survey Family Study. Nine waves of data were used to create latent growth trajectories and test for associations between trajectory class and 5HTTLPR genotype.

Results: For the full sample, 5HTTLPR was not associated with conduct problem phenotypes. However, the short (s) allele was associated with chronic conduct problems in females; a nominally significant sex by 5HTTLPR genotype interaction was noted.

Conclusion: Longitudinal studies provide unique opportunities for phenotypic refinement and such techniques, with large samples, may be useful for phenotypic definition with other study designs, such as whole genome association studies.

aUniversity of Colorado Denver, Aurora, Colorado

bUniversity of Colorado, Boulder, Colorado

cSam Houston State University, Huntsville, Texas

dUnited BioSource Corporation, Bethesda, Maryland, USA

Correspondence to Joseph T. Sakai, MD, University of Colorado School of Medicine, 12469 East 17th Place, Bldg. 400, PO Box 6508, Mail Stop F478, Aurora, CO 80045, USA

Tel: +303 724 3182; fax: +303 724 3178;

e-mail: joseph.sakai@ucdenver.edu

Received 14 January 2009 Revised 16 November 2009 Accepted 1 January 2010

© 2010 Lippincott Williams & Wilkins, Inc.