title: A two-stage case-control association study of PADI2 with schizophrenia.
abstract: Peptidylarginine deiminases (PADIs), five isoforms of which have been identified, catalyze the conversion of arginine residues to citrulline residues in proteins. Recent studies have revealed that abnormal activation of PADI2, the gene for which is expressed throughout the nervous system, is likely to be related to the pathogenesis of neuropsychiatric diseases with neurodegenerative processes, such as Alzheimer's disease and multiple sclerosis. Such a progressive neurodegenerative process could be involved in the etiology and/or course of schizophrenia, and PADI2 may be a candidate gene for schizophrenia. To assess whether PADI2 has a role in vulnerability to schizophrenia, we conducted a two-stage case-control association study in Japanese individuals. In a screening population of 534 patients and 559 control individuals, we examined eight single-nucleotide polymorphisms (SNPs) including four haplotype tag SNPs and four coding SNPs in PADI2. There was a potential association of a synonymous SNP in exon 7 with schizophrenia. However, we could not replicate this association in a confirmatory population of 2126 patients and 2228 control individuals. The results of this study suggest that PADI2 does not contribute to genetic susceptibility to schizophrenia.
authors.affiliation: Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan. yuichiro@med.niigata-u.ac.jp
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Ayako
authors.initials: A
authors.lastname: Nunokawa
authors.forename: Naoshi
authors.initials: N
authors.lastname: Kaneko
authors.forename: Tadao
authors.initials: T
authors.lastname: Arinami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otowa
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
mesh_terms: D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics*
chemical_list: D006867:Hydrolases; C000620352:PADI2 protein, human; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases