Association of tagging single nucleotide polymorphisms on 8 candidate genes in dopaminergic pathway with schizophrenia in Croatian population.
OBJECTIVE
To perform a comprehensive evaluation of association of common genetic variants in candidate genes in the dopaminergic pathway with schizophrenia in a sample from Croatian population.


METHODS
A case-control association study was performed on 104 unrelated patients with schizophrenia recruited from a psychiatric hospital in Zagreb and 131 phenotypically normal Croatian subjects. Forty-nine tagging single nucleotide polymorphisms (tagSNPs) in 8 candidate genes in the dopaminergic pathway were identified from the HapMap database and tested for association. Genotyping was performed using the SNPlex platform. Statistical analysis was conducted to assess allelic and genotypic associations between cases and controls using a goodness of fit chi(2) test and trend test, respectively; adjustment for multiple testing was done by permutation based analysis.


RESULTS
Significant allele frequency differences between schizophrenia cases and controls were observed at 4 tagSNPs located in the genes DRD5, HTR1B1, DBH, and TH1 (P<0.005). A trend test also confirmed the genotypic association (P<0.001) of these 4 tagSNPs. Additionally, moderate association (P<0.05) was observed with 8 tagSNPs on SLC6A3, DBH, DRD4, SLC6A4, and COMT.


CONCLUSIONS
Common genetic variants in genes involved in the dopaminergic pathway are associated with schizophrenia in the populations of Caucasian descent.
Pal
Prodipto
P
Department of Environmental Health, Center for Genome Information, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Mihanović
Mate
M
Molnar
Sven
S
Xi
Huifeng
H
Sun
Guangyun
G
Guha
Saurav
S
Jeran
Nina
N
Tomljenović
Andrea
A
Malnar
Ana
A
Missoni
Sasa
S
Deka
Ranjan
R
Rudan
Pavao
P
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D017523:Croatia; D030541:Databases, Genetic; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011954:Receptors, Dopamine / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*
D011954:Receptors, Dopamine; D004298:Dopamine