Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia

Ryoko Higashiyama, Tohru Ohnuma, Yuto Takebayashi, Ryo Hanzawa, Nobuto Shibata, Hidenaga Yamamori, Yuka Yasuda, Itaru Kushima, Branko Aleksic, Kenji Kondo, Masashi Ikeda, Ryota Hashimoto, Nakao Iwata, Norio Ozaki, Heii Arai

研究成果: Article

6 引用 (Scopus)

抄録

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 (χ 2 =8.327, P=0.0039), CNV6 (χ 2 =19.66, P=0.00005), and CNV8 (χ 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.

元の言語English
ページ(範囲)447-457
ページ数11
ジャーナルAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
171
発行部数3
DOI
出版物ステータスPublished - 01-04-2016

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DNA Copy Number Variations
Catechol O-Methyltransferase
Genetic Promoter Regions
Schizophrenia
Single Nucleotide Polymorphism
DiGeorge Syndrome
Exons
Sample Size
Chromosome Deletion
Rare Diseases
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

これを引用

Higashiyama, Ryoko ; Ohnuma, Tohru ; Takebayashi, Yuto ; Hanzawa, Ryo ; Shibata, Nobuto ; Yamamori, Hidenaga ; Yasuda, Yuka ; Kushima, Itaru ; Aleksic, Branko ; Kondo, Kenji ; Ikeda, Masashi ; Hashimoto, Ryota ; Iwata, Nakao ; Ozaki, Norio ; Arai, Heii. / 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. 2016 ; 巻 171, 番号 3. pp. 447-457.
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title = "Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia",
abstract = "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 (χ 2 =8.327, P=0.0039), CNV6 (χ 2 =19.66, P=0.00005), and CNV8 (χ 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.",
author = "Ryoko Higashiyama and Tohru Ohnuma and Yuto Takebayashi and Ryo Hanzawa and Nobuto Shibata and Hidenaga Yamamori and Yuka Yasuda and Itaru Kushima and Branko Aleksic and Kenji Kondo and Masashi Ikeda and Ryota Hashimoto and Nakao Iwata and Norio Ozaki and Heii Arai",
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Higashiyama, R, Ohnuma, T, Takebayashi, Y, Hanzawa, R, Shibata, N, Yamamori, H, Yasuda, Y, Kushima, I, Aleksic, B, Kondo, K, Ikeda, M, Hashimoto, R, Iwata, N, Ozaki, N & Arai, H 2016, '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, 番号 3, pp. 447-457. https://doi.org/10.1002/ajmg.b.32426

Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia. / Higashiyama, Ryoko; Ohnuma, Tohru; Takebayashi, Yuto; Hanzawa, Ryo; Shibata, Nobuto; Yamamori, Hidenaga; Yasuda, Yuka; Kushima, Itaru; Aleksic, Branko; Kondo, Kenji; Ikeda, Masashi; Hashimoto, Ryota; Iwata, Nakao; Ozaki, Norio; Arai, Heii.

:: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 巻 171, 番号 3, 01.04.2016, p. 447-457.

研究成果: Article

TY - JOUR

T1 - Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia

AU - Higashiyama, Ryoko

AU - Ohnuma, Tohru

AU - Takebayashi, Yuto

AU - Hanzawa, Ryo

AU - Shibata, Nobuto

AU - Yamamori, Hidenaga

AU - Yasuda, Yuka

AU - Kushima, Itaru

AU - Aleksic, Branko

AU - Kondo, Kenji

AU - Ikeda, Masashi

AU - Hashimoto, Ryota

AU - Iwata, Nakao

AU - Ozaki, Norio

AU - Arai, Heii

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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 (χ 2 =8.327, P=0.0039), CNV6 (χ 2 =19.66, P=0.00005), and CNV8 (χ 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.

AB - 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 (χ 2 =8.327, P=0.0039), CNV6 (χ 2 =19.66, P=0.00005), and CNV8 (χ 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.

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