Replication and cross‐phenotype study based upon schizophrenia GWASs data in the Japanese population: Support for association of MHC region with psychosis. Issue 5 (29th May 2014)

• Record Type: Journal Article
• Authors: Saito, Takeo; Kondo, Kenji; Iwayama, Yoshimi; Shimasaki, Ayu; Aleksic, Branko; Yamada, Kazuo; Toyota, Tomoko; Hattori, Eiji; Esaki, Kosei; Ujike, Hiroshi; Inada, Toshiya; Kunugi, Hiroshi; Kato, Tadafumi; Yoshikawa, Takeo; Ozaki, Norio; Ikeda, Masashi; Iwata, Nakao
• Is Part Of: American journal of medical genetics. Volume 165:Issue 5(2014)
• Page Start: 421
• Page End: 427
• Publication Date: 2014-05-29
• Subjects: Neuropsychiatry -- Periodicals; Medical genetics -- Periodicals; 616.8904205
• DOI: 10.1002/ajmg.b.32246
• Languages: English
• ISSNs: 1552-4841

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmgb32246-sec-0001" sec-type="section"> <p>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<sub>uncorrected</sub> < 0.05), of which two SNPs located in the major histocompatibility complex region (rs7759855 in <italic>zinc finger and SCAN domain containing 31</italic> [<italic>ZSCAN31</italic>] and rs1736913 in <italic>HLA‐F antisense RNA1</italic> [<italic>HLA‐F‐AS1</italic>]) were further assessed in the second‐set replication samples. The associations were confirmed for rs7759855 (P<sub>corrected</sub> = 0.026 for psychosis; P<sub>corrected</sub> = 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 <italic>ZSCAN31</italic> (rs7759855) had the strongest association with the phenotypes (best <italic>P</italic> = 6.8 × 10<sup>−5</sup> 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. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>