TY - JOUR
T1 - A possible association between schizophrenia and GRIK3 polymorphisms in a multicenter sample of Scandinavian origin (SCOPE)
AU - Djurovic, S
AU - Kähler, A K
AU - Kulle, B
AU - Jönsson, E G
AU - Agartz, I
AU - Le Hellard, S
AU - Hall, H
AU - Jakobsen, Klaus Damgaard
AU - Hansen, Thomas Folkmann
AU - Melle, I
AU - Werge, T
AU - Steen, V M
AU - Andreassen, O A
N1 - Keywords: Adult; Alleles; Chromosomes, Human, Pair 1; Female; Genetic Markers; Genotype; Haplotypes; Humans; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Psychotic Disorders; Receptors, Kainic Acid; Scandinavia; Schizophrenia; Schizophrenic Psychology
PY - 2009
Y1 - 2009
N2 - There is considerable evidence of altered glutamatergic signalling in schizophrenia and a polymorphic variant of the GRIK3 glutamate receptor gene on 1p34-33 has previously been associated to this psychotic disorder. We therefore conducted a systematic association study with 30 HapMap-selected tagging SNPs across GRIK3 in three independent samples of Scandinavian origin from the Scandinavian Collaboration of Psychiatric Etiology (SCOPE), including a total of 839 cases with schizophrenia spectrum and 1473 healthy controls. Four markers (rs6671364, rs17461259, rs472188, and rs535620) attained nominally significant P-values in both the genotypic (0.002, 0.02, 0.03, and 0.05, respectively) and allelic (0.001, 0.006, 0.03, and 0.02, respectively) association tests for the combined sample, and 2 additional markers (rs481047and rs1160751) displayed significance for the genotype (P-values: 0.03 and 0.04). Several haplotypes, that all included at least one of the four SNPs implicated by the single marker analysis, remained significant after adjustment for multiple testing using permutations with 10,000 shuffles. In addition we observed an association for two of the four significant GRIK3 markers (rs472188 and rs535620) to scores for negative symptoms on the PANSS scale. The present results, although not robust, support the importance of more extensive investigations of GRIK3, given its potential role in mediating risk for schizophrenia.
AB - There is considerable evidence of altered glutamatergic signalling in schizophrenia and a polymorphic variant of the GRIK3 glutamate receptor gene on 1p34-33 has previously been associated to this psychotic disorder. We therefore conducted a systematic association study with 30 HapMap-selected tagging SNPs across GRIK3 in three independent samples of Scandinavian origin from the Scandinavian Collaboration of Psychiatric Etiology (SCOPE), including a total of 839 cases with schizophrenia spectrum and 1473 healthy controls. Four markers (rs6671364, rs17461259, rs472188, and rs535620) attained nominally significant P-values in both the genotypic (0.002, 0.02, 0.03, and 0.05, respectively) and allelic (0.001, 0.006, 0.03, and 0.02, respectively) association tests for the combined sample, and 2 additional markers (rs481047and rs1160751) displayed significance for the genotype (P-values: 0.03 and 0.04). Several haplotypes, that all included at least one of the four SNPs implicated by the single marker analysis, remained significant after adjustment for multiple testing using permutations with 10,000 shuffles. In addition we observed an association for two of the four significant GRIK3 markers (rs472188 and rs535620) to scores for negative symptoms on the PANSS scale. The present results, although not robust, support the importance of more extensive investigations of GRIK3, given its potential role in mediating risk for schizophrenia.
U2 - 10.1016/j.schres.2008.10.010
DO - 10.1016/j.schres.2008.10.010
M3 - Journal article
C2 - 19022628
SN - 0920-9964
VL - 107
SP - 242
EP - 248
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 2-3
ER -