Epistasis between neurochemical gene polymorphisms and risk for ADHD

Segurado, Ricardo, Bellgrove, Mark A, Manconi, Francesca, Gill, Michael and Hawi, Ziarah (2011) Epistasis between neurochemical gene polymorphisms and risk for ADHD. European Journal of Human Genetics, 19 5: 577-582. doi:10.1038/ejhg.2010.250

Author Segurado, Ricardo
Bellgrove, Mark A
Manconi, Francesca
Gill, Michael
Hawi, Ziarah
Title Epistasis between neurochemical gene polymorphisms and risk for ADHD
Journal name European Journal of Human Genetics   Check publisher's open access policy
ISSN 1018-4813
Publication date 2011-05
Sub-type Article (original research)
DOI 10.1038/ejhg.2010.250
Volume 19
Issue 5
Start page 577
End page 582
Total pages 6
Place of publication London, Hamps, U.K.
Publisher Nature Publishing Group
Collection year 2012
Language eng
Formatted abstract
A number of genes with function related to synaptic neurochemistry have been genetically associated with attention deficit/hyperactivity disorder. However, susceptibility to the development of common psychiatric disorders by single variants acting alone, can so far only explain a small proportion of the heritability of the phenotype. It has been postulated that the unexplained ‘dark heritability’ may at least in part be due to epistatic effects, which may account for the small observed marginal associations, and the difficulties with replication of positive findings. We undertook a comprehensive exploration of pair-wise interactions between genetic variants in 24 candidate genic regions involved in monoaminergic catabolism, anabolism, release, re-uptake and signal transmission in a sample of 177 parent-affected child trios using a case-only design and a case–pseudocontrol design using conditional logistic regression. Marker-pairs thresholded on interaction odds ratio (OR) and P-value are presented. We detected a number of interaction ORs >4.0, including an interesting correlation between markers in the ADRA1B and DBH genes in affected individuals, and several further interesting but smaller effects. These effects are no larger than you would expect by chance under the assumption of independence of all pair-wise relations; however, independence is unlikely. Furthermore, the size of these effects is of interest and attempts to replicate these results in other samples are anticipated.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2012 Collection
School of Psychology Publications
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
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Created: Thu, 20 Oct 2011, 17:30:54 EST by Ziarih Hawi on behalf of Queensland Brain Institute