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Replication and cross‐phenotype study based upon schizophrenia GWASs data in the Japanese population: Support for association of MHC region with psychosis
Author(s) -
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
Publication year - 2014
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32246
Subject(s) - single nucleotide polymorphism , genome wide association study , genetic association , genetics , population , snp , schizophrenia (object oriented programming) , biology , psychosis , allele , medicine , genotype , gene , psychiatry , environmental health
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. © 2014 Wiley Periodicals, Inc.