Epistasis between neurochemical gene polymorphisms and risk for ADHD

Ricardo Segurado (1) , Mark A Bellgrove (1) , Francesca Manconi (1) , Micheal Gill (1) , Dr. Hawi (1)

1 Department of Psychiatry

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 genes 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 and p-value are presented. We detected a number of interaction odds ratios greater than 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.

Mots clés: ADHD; epistasis; candidate gene

Ricardo Segurado, Mark A Bellgrove, Francesca Manconi, Micheal Gill, Dr. Hawi. Epistasis between neurochemical gene polymorphisms and risk for ADHD. European Journal of Human Genetics, 2011, ⟨10.1038/ejhg.2010.250⟩. ⟨hal-00611251⟩