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Title of Journal: Hum Genet

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Abbravation: Human Genetics

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Springer-Verlag

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DOI

10.1016/0022-328x(86)80039-0

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1432-1203

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Association study of the Emphasis Type="Italic"K

Authors: Kazuo Yamada Yoshimi Iwayama Tomoko Toyota Tetsuo Ohnishi Hisako Ohba Motoko Maekawa Takeo Yoshikawa
Publish Date: 2011/09/17
Volume: 131, Issue: 3, Pages: 443-451
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Abstract

We recently reported the results of a genomewide association study GWAS of schizophrenia in the Japanese population In that study a single nucleotide polymorphism SNP rs3106653 in the KCNJ3 potassium inwardly rectifying channel subfamily J member 3 gene located at 2q241 showed association with schizophrenia in two independent sample sets KCNJ3 also termed GIRK1 or Kir31 is a member of the G proteinactivated inwardly rectifying K+ channel GIRK group GIRKs are widely distributed in the brain and play an important role in regulating neural excitability through the activation of various G proteincoupled receptors In this study we set out to examine this association using a different population We first performed a genecentric association study of the KCNJ3 gene by genotyping 38 tagSNPs in the Chinese population We detected nine SNPs that displayed significant association with schizophrenia lowest P = 00016 for rs3106658 Global significance = 0036 The initial marker SNP rs3106653 examined in our prior GWAS in the Japanese population also showed nominally significant association in the Chinese population P = 0028 Next we analyzed transcript levels in the dorsolateral prefrontal cortex of postmortem brains from patients with schizophrenia and bipolar disorder and from healthy controls using realtime quantitative RTPCR We found significantly lower KCNJ3 expression in postmortem brains from schizophrenic and bipolar patients compared with controls These data suggest that the KCNJ3 gene is genetically associated with schizophrenia in Asian populations and add further evidence to the “channelopathy theory of psychiatric illnesses”

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