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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)
journal contribution
posted on 2007-10-01, 00:00 authored by Craig OlssonCraig Olsson, G Byrnes, R Anney, V Collins, Sheryl Hemphill, R Williamson, G PattonWe 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.
History
Journal
Genes, brain and behaviourVolume
6Issue
7Pagination
647 - 652Publisher
Wiley - Blackwell PublishingLocation
Malden, Mass.Publisher DOI
ISSN
1601-1848eISSN
1601-183XLanguage
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2007, Murdoch Childrens Research InstituteUsage metrics
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adolescenceanxietyCOMTgene–gene interactiongene–environment interaction5HTTLPRlongitudinalScience & TechnologyLife Sciences & BiomedicineBehavioral SciencesNeurosciencesNeurosciences & Neurologygene-gene interactiongene-environment interactionCATECHOL-O-METHYLTRANSFERASEHUMAN SEROTONIN TRANSPORTERALLELIC VARIATIONPOLYMORPHISMGENEASSOCIATIONPHARMACOGENETICSPOPULATIONGENOTYPEDISORDER
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