title: Replication and cross-phenotype study based upon schizophrenia GWASs data in the Japanese population: support for association of MHC region with psychosis.
abstract: Recent genome-wide association studies (GWASs) of schizophrenia (SCZ) identified several susceptibility genes and suggested shared genetic components between SCZ and bipolar disorder (BD). We conducted a genetic association study of single nucleotide polymorphisms (SNPs) selected according to previous SCZ GWAS targeting psychotic disorders (SCZ and BD) in the Japanese population. Fifty-one SNPs were analyzed in a two-stage design using first-set screening samples (all SNPs: 1,032 SCZ, 1,012 BD, and 993 controls) and second-set replication samples ("significant" SNPs in the first-set screening analysis: 1,808 SCZ, 821 BD, and 2,321 controls). We assessed allelic associations between the selected SNPs and the three phenotypes (SCZ, BD, and "psychosis" [SCZ + BD]). Nine SNPs revealed nominal association signals for all comparisons (P(uncorrected) < 0.05), of which two SNPs located in the major histocompatibility complex region (rs7759855 in zinc finger and SCAN domain containing 31 [ZSCAN31] and rs1736913 in HLA-F antisense RNA1 [HLA-F-AS1]) were further assessed in the second-set replication samples. The associations were confirmed for rs7759855 (P(corrected) = 0.026 for psychosis; P(corrected) = 0.032 for SCZ), although the direction of effect was opposite to that in the original GWAS of the Chinese population. Finally, a meta-analysis was conducted using our two samples and using our data and data from Psychiatric GWAS Consortium (PGC), which have shown the same direction of effect. SNP in ZSCAN31 (rs7759855) had the strongest association with the phenotypes (best P = 6.8 × 10(-5) for psychosis: present plus PGC results). These data support shared risk SNPs between SCZ and BD in the Japanese population and association between MHC and psychosis.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Kondo
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Ayu
authors.initials: A
authors.lastname: Shimasaki
authors.forename: Branko
authors.initials: B
authors.lastname: Aleksic
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Eiji
authors.initials: E
authors.lastname: Hattori
authors.forename: Kosei
authors.initials: K
authors.lastname: Esaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Kato
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006649:Histocompatibility Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D006649:Histocompatibility Antigens
keywords: bipolar disorder; genome-wide association study; major histocompatibility complex; single nucleotide polymorphism