Original scientific paper
Association of Tagging Single Nucleotide Polymorphisms on 8 Candidate Genes in Dopaminergic Pathway with Schizophrenia in Croatian Population
Prodipto Pal
; Department of Enviromental Health, Center for Genome Information, University of Cincinnati, OH, USA
Mate Mihanović
; St. Ivan Psychiatric Hospital, Zagreb, Croatia
Sven Molnar
; St. Ivan Psychiatric Hospital, Zagreb, Croatia
Huifeng Xi
; Department of Enviromental Health, Center for Genome Information, University of Cincinnati, OH, USA
Guangyun Sun
; Department of Enviromental Health, Center for Genome Information, University of Cincinnati, OH, USA
Saurav Guha
; Department of Enviromental Health, Center for Genome Information, University of Cincinnati, OH, USA
Nina Jeran
; Institute for Anthropological Research, Zagreb, Croatia
Andrea Tomljenović
; Institute for Anthropological Research, Zagreb, Croatia
Ana Malnar
; Institute for Anthropological Research, Zagreb, Croatia
Saša Missoni
; Institute for Anthropological Research, Zagreb, Croatia
Ranjan Deka
; Department of Enviromental Health, Center for Genome Information, University of Cincinnati, OH, USA
Pavao Rudan
; Institute for Anthropological Research, Zagreb, Croatia
Abstract
Aim 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
χ2 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 tag-
SNPs 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.
Keywords
Schizophrenia; candidate genes; dopamine pathway; tagging SNPs; allelic association; Croatian population
Hrčak ID:
47856
URI
Publication date:
15.8.2009.
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