Effect of the G72 (DAOA) putative risk haplotype on cognitive functions in healthy subjects

Andreas Jansen,Axel Krug,Marcella Rietschel,Valentin Markov,Markus Thimm,Tilo Kircher,Jens Treutlein,Sören Krach,Markus M Nöthen,Klaus Zerres,Thomas Eggermann

doi:10.1186/1471-244x-9-60

Abstract

BackgroundIn the last years, several susceptibility genes for psychiatric disorders have been identified, among others G72 (also named D-amino acid oxidase activator, DAOA). Typically, the high-risk variant of a vulnerability gene is associated with decreased cognitive functions already in healthy individuals. In a recent study however, a positive effect of the high-risk variant of G72 on verbal working memory was reported. In the present study, we therefore examined the relationship between G72 genotype status and a broad range of cognitive functions in 423 healthy individuals.MethodsThe G72 carrier status was assessed by the two single nucleotide polymorphisms (SNPs) M23 and M24. Subjects were divided into three risk groups (low, intermediate and high risk).ResultsG72 status influenced a number of cognitive functions, such as verbal working memory, attention, and, at a trend level, spatial working memory and executive functions. Interestingly, the high-risk allele carriers scored better than one or even both other groups.ConclusionOur data show that the putative high-risk haplotype (i.e. homozygote C/C-allele carriers in SNP M23 and homozygote T/T-allele carriers in SNP M24) is in healthy individuals not necessarily associated with worse performance in cognitive functions, but even with better performance in some domains. Further work is required to identify the mechanisms of G72 on brain functions.

Highlights

In the last years, several susceptibility genes for psychiatric disorders have been identified, among others G72
The high risk variant of G72 has a beneficial influence on verbal working memory in healthy subjects, it is known to increase the risk for schizophrenia and affective disorders, diseases that are associated with impairments in this domain [2,3,5,6]
We examined whether the positive influence of the high risk G72 variant is restricted to verbal working memory or whether this genotype beneficially influences other cognitive domains

Summary

Introduction

Several susceptibility genes for psychiatric disorders have been identified, among others G72 ( named D-amino acid oxidase activator, DAOA). Among the different cognitive domains, verbal memory, verbal fluency and attention are typically most affected [2,3,5,6] In schizophrenia, these impairments are already present in adolescence, long before the onset of psychotic symptoms [4,6], in the prodromal state [7] and can be found in relatives of patients [8,9], suggesting a genetic influence. The high risk variant of G72 has a beneficial influence on verbal working memory in healthy subjects, it is known to increase the risk for schizophrenia and affective disorders, diseases that are associated with impairments in this domain [2,3,5,6]

Methods

Results

Discussion

Conclusion