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COMT Val158Met and 5HTTLPR functional loci interact to predict anxiety across adolescence : results from the Victorian Adolescent Health Cohort Study (1992-2006)

Olsson, C. A., Byrnes, G. B., Anney, R. J. L., Collins, V., Hemphill, S. A., Williamson, R. and Patton, G. C. 2007, COMT Val158Met and 5HTTLPR functional loci interact to predict anxiety across adolescence : results from the Victorian Adolescent Health Cohort Study (1992-2006), Genes, brain and behaviour, vol. 6, no. 7, pp. 647-652, doi: 10.1111/j.1601-183X.2007.00313.x.

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Title COMT Val158Met and 5HTTLPR functional loci interact to predict anxiety across adolescence : results from the Victorian Adolescent Health Cohort Study (1992-2006)
Author(s) Olsson, C. A.ORCID iD for Olsson, C. A. orcid.org/0000-0002-5927-2014
Byrnes, G. B.
Anney, R. J. L.
Collins, V.
Hemphill, S. A.
Williamson, R.
Patton, G. C.
Journal name Genes, brain and behaviour
Volume number 6
Issue number 7
Start page 647
End page 652
Publisher Wiley - Blackwell Publishing
Place of publication Malden, Mass.
Publication date 2007-10
ISSN 1601-1848
1601-183X
Keyword(s) adolescence
anxiety
COMT
gene–gene interaction
gene–environment interaction
5HTTLPR
longitudinal
Summary We investigated whether a composite genetic factor, based on the combined actions of catechol-O-methyltransferase (COMT) (Val158Met) and serotonin transporter (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight-wave longitudinal study of mental health and well-being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose–response reductions in the odds of reporting persisting generalized (free-floating) anxiety across adolescence were observed for the COMT Met158 [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76–0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79–0.99, P = 0.033). There was no evidence for a dose–response interaction effect between loci. However, there was a double-recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29–0.70, P < 0.001) among carriers homozygous for both the COMT Met158 and the 5HTTLPR Short alleles (Met158Met + Short-Short) compared with the remaining cohort. The double-recessive effect remained after multivariate adjustment for a range of psychosocial predictors of anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.
Language eng
DOI 10.1111/j.1601-183X.2007.00313.x
Field of Research 179999 Psychology and Cognitive Sciences not elsewhere classified
Socio Economic Objective 970117 Expanding Knowledge in Psychology and Cognitive Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2007, Murdoch Childrens Research Institute
Persistent URL http://hdl.handle.net/10536/DRO/DU:30041320

Document type: Journal Article
Collection: School of Psychology
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