Open AccessCOMT Val 158 Met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence: results from the Victorian Adolescent Health Cohort Study
Author(s) -
Olsson C. A.,
Byrnes G. B.,
Anney R. J. L.,
Collins V.,
Hemphill S. A.,
Williamson R.,
Patton G. C.
Publication year - 2007
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2007.00313.x
Subject(s) - anxiety , psychosocial , psychology , odds ratio , cohort , mental health , rs4680 , confidence interval , clinical psychology , medicine , demography , allele , catechol o methyl transferase , psychiatry , genetics , gene , biology , sociology
We investigated whether a composite genetic factor, based on the combined actions of catechol‐ O ‐methyltransferase ( COMT ) (Val 158 Met) 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 Met 158 [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 Met 158 and the 5HTTLPR Short alleles (Met 158 Met + 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.