Common variants in MAGI2 gene are associated with increased risk for cognitive impairment in schizophrenic patients.
Schizophrenia is a complex psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive impairment. MAGI2, a relatively large gene (∼1.5 Mbps) that maps to chromosome 7q21, is involved in recruitment of neurotransmitter receptors such as AMPA- and NMDA-type glutamate receptors. A genetic association study designed to evaluate the association between MAGI2 and cognitive performance or schizophrenia has not been conducted. In this case-control study, we examined the relationship of single nucleotide polymorphism (SNP) variations in MAGI2 and risk for schizophrenia in a large Japanese sample and explored the potential relationships between variations in MAGI2 and aspects of human cognitive function related to glutamate activity. Based on the result of first schizophrenia genome-wide association study in a Japanese population (JGWAS), we selected four independent SNPs and performed an association study using a large independent Japanese sample set (cases 1624, controls 1621). Wisconsin Card Sorting Test (WCST) was used to evaluate executive function in 114 cases and 91 controls. We found suggestive evidence for genetic association of common SNPs within MAGI2 locus and schizophrenia in Japanese population. Furthermore in terms of association between MAGI2 and cognitive performance, we observed that genotype effect of rs2190665 on WCST score was significant (p = 0.034) and rs4729938 trended toward significance (p = 0.08). In conclusion, although we could not detect strong genetic evidence for association of common variants in MAGI2 and increased schizophrenia risk in a Japanese population, these SNPs may increase risk of cognitive impairment in schizophrenic patients.
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takayoshi
T
Koide
Masahiro
M
Banno
Branko
B
Aleksic
Saori
S
Yamashita
Tsutomu
T
Kikuchi
Kunihiro
K
Kohmura
Yasunori
Y
Adachi
Naoko
N
Kawano
Itaru
I
Kushima
Yukako
Y
Nakamura
Takashi
T
Okada
Masashi
M
Ikeda
Kazutaka
K
Ohi
Yuka
Y
Yasuda
Ryota
R
Hashimoto
Toshiya
T
Inada
Hiroshi
H
Ujike
Tetsuya
T
Iidaka
Michio
M
Suzuki
Masatoshi
M
Takeda
Nakao
N
Iwata
Norio
N
Ozaki
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018698:Glutamic Acid / Q000235:genetics; D051528:Guanylate Kinases; D006801:Humans; D007564:Japan; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000150:complications* / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018698:Glutamic Acid; D051528:Guanylate Kinases; C485777:MAGI2 protein, human