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


METHODS
The 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).


RESULTS
G72 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.


CONCLUSIONS
Our 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.
Section of BrainImaging, Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany. an.jan@gmx.de
Andreas
A
Jansen
Sören
S
Krach
Axel
A
Krug
Valentin
V
Markov
Thomas
T
Eggermann
Klaus
K
Zerres
Markus
M
Thimm
Markus M
MM
Nöthen
Jens
J
Treutlein
Marcella
M
Rietschel
Tilo
T
Kircher
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001921:Brain / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics / Q000502:physiology; D005838:Genotype; D006239:Haplotypes / Q000235:genetics* / Q000502:physiology; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins