2016年4月
Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
- 巻
- 171
- 号
- 3
- 開始ページ
- 447
- 終了ページ
- 457
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1002/ajmg.b.32426
- 出版者・発行元
- WILEY-BLACKWELL
Chromosome 22q11.2 deletion syndrome and genetic variations including single-nucleotide polymorphism (SNP) and copy number variation (CNV) in catechol-O-methyltransferase (COMT) situated at 22q11.2 remains controversial. Here, the genetic relationship between COMT and Japanese patients with schizophrenia was investigated by examining whether the SNPs correlated with schizophrenia based on a common disease-common variant hypothesis. Additionally, 22q11.2DS were screened based on a common disease-rare variant hypothesis; low-frequency CNVs situated at two COMT promoters and exons were investigated based on the low-frequency variants with an intermediate effect; and positive findings from the first stage were reconfirmed using a second-stage replication study including a larger sample size. Eight SNPs and 10 CNVs were investigated using Taqman SNP and CNV quantitative real-time polymerase chain reaction method. For the first-stage analysis, 513 unrelated Japanese patients with schizophrenia and 705 healthy controls were examined. For the second-stage replication study, positive findings from the first stage were further investigated using a larger sample size, namely 1,854 patients with schizophrenia and 2,137 controls. The first-stage analysis showed significant associations among schizophrenia, intronic SNP rs165774, CNV6 situated at promoter 1, CNV8 at exon 6, and CNV9 at exon 7. The second-stage study showed that intronic SNP rs165774 ((2)=8.327, P=0.0039), CNV6 ((2)=19.66, P=0.00005), and CNV8 ((2)=16.57, P=0.00025) were significantly associated with schizophrenia. Large and rare CNVs as well as low-frequency CNVs and relatively small CNVs, namely <30kb in COMT, may be genetic risk factors for schizophrenia. (c) 2016 Wiley Periodicals, Inc.
- リンク情報
- ID情報
-
- DOI : 10.1002/ajmg.b.32426
- ISSN : 1552-4841
- eISSN : 1552-485X
- PubMed ID : 26852906
- Web of Science ID : WOS:000373029100015