Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia.
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 <30 kb in COMT, may be genetic risk factors for schizophrenia.
['Higashiyama|Ryoko|R|', 'Ohnuma|Tohru|T|', 'Takebayashi|Yuto|Y|', 'Hanzawa|Ryo|R|', 'Shibata|Nobuto|N|', 'Yamamori|Hidenaga|H|', 'Yasuda|Yuka|Y|', 'Kushima|Itaru|I|', 'Aleksic|Branko|B|', 'Kondo|Kenji|K|', 'Ikeda|Masashi|M|', 'Hashimoto|Ryota|R|', 'Iwata|Nakao|N|', 'Ozaki|Norio|N|', 'Arai|Heii|H|']
D000328:Adult D044466:Asians D016022:Case-Control Studies D002394:Catechol O-Methyltransferase D056915:DNA Copy Number Variations D005260:Female D056726:Genetic Association Studies D020022:Genetic Predisposition to Disease D006239:Haplotypes D006801:Humans D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D011401:Promoter Regions, Genetic D014176:Protein Biosynthesis D060888:Real-Time Polymerase Chain Reaction D015203:Reproducibility of Results D012559:Schizophrenia
schizophrenia 22q11.2 single-nucleotide polymorphism copy number variation catechol-O-methyltransferase