한국인 조현병 집단에서 에스트로겐 대사(ESR1, COMT) 유전자의 가족연합분석: 예비연구
A Family-Based Association Analysis of Estrogen Metabolism (ESR1, COMT) Gene in a Korean Population with Schizophrenia: A Pilot Study
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Objectives：A recent study of a European sample implied that the 14 genes previously known to be related with schizophrenia may play little roles. But much work remains before dismissing these genes from their connection to schizophrenia. This is a pilot study for family based association test (FBAT) analysis of estrogen metabolism gene in a Korean population with schizophrenia. Methods：27 probands with schizophrenia were recruited with their parents and siblings. The subjects were interviewed using Korean versions of diagnostic interview for genetic studies and family interview for genetic studies. We analyzed 2 single nucleotide polymorphism (SNP) of ESR1, COMT gene. We performed FBAT and linkage disequilibrium analyses for each individual SNP. Results：We found a significant SNP of ESR1 gene in chromosome 6 for the qualitative phenotype of schizophrenia. That result was replicated for the quantitative phenotype of apparent onset, apparent onset of psychosis, and first treatment age. We also found a significant SNP of ESR1 gene in chromosome 6 for the quantitative phenotype of any delusions. Conclusions：Our results show that quantitative traits such as age of onset, any delusions, and any hallucinations could be continuous with qualitative trait in schizophrenia. But we should be very cautious because there are clear limitations in some nominal number of SNPs and the small incomplete pedigrees. In the future, FBAT analyses in families with subtyped schizophrenic probands according to personality, working memory, cognition will facilitate fine mapping analyses for searching candidate genes of schizophrenia.
Abstract
Objectives：A recent study of a European sample implied that the 14 genes previously known to be related with schizophrenia may play little roles. But much work remains before dismissing these genes from their connection to schizophrenia. This is a pilot study for family based association test (FBAT) analysis of estrogen metabolism gene in a Korean population with schizophrenia. Methods：27 probands with schizophrenia were recruited with their parents and siblings. The subjects were interviewed using Korean versions of diagnostic interview for genetic studies and family interview for genetic studies. We analyzed 2 single nucleotide polymorphism (SNP) of ESR1, COMT gene. We performed FBAT and linkage disequilibrium analyses for each individual SNP. Results：We found a significant SNP of ESR1 gene in chromosome 6 for the qualitative phenotype of schizophrenia. That result was replicated for the quantitative phenotype of apparent onset, apparent onset of psychosis, and first treatment age. We also found a significant SNP of ESR1 gene in chromosome 6 for the quantitative phenotype of any delusions. Conclusions：Our results show that quantitative traits such as age of onset, any delusions, and any hallucinations could be continuous with qualitative trait in schizophrenia. But we should be very cautious because there are clear limitations in some nominal number of SNPs and the small incomplete pedigrees. In the future, FBAT analyses in families with subtyped schizophrenic probands according to personality, working memory, cognition will facilitate fine mapping analyses for searching candidate genes of schizophrenia.
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