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.

Reduced cortical thickness related to single nucleotide polymorphisms in the major histocompatibility complex region in antipsychotic‐naive schizophrenia

“…Moreover, schizophrenia and other neuropsychiatric disorders are associated with the dysregulation of NCAM in the hippocampus, cortex, and subcortical structures (Marquis, ). Regarding the other four SNPs, that is, rs1736913, rs204999, rs2021722, and rs2523722, they also exhibited significant relationships with schizophrenia in this study, consistent with the results of previous studies (Corvin & Morris, ; Irish Schizophrenia Genomics Consortium, ; Saito et al, ). Our findings extend those of previous studies by directly supporting the associations between MHC variants and cortical thickness in schizophrenia patients in vivo.…”

Genome‐wide association studies of bipolar disorder: A systematic review of recent findings and their clinical implications

“…Briefly, epidemiologic surveys have shown increased prevalences of SCZ and BD in the first‐degree relatives of the probands of SCZ or BD . Furthermore, GWAS results supported this observation on the basis of an SNP association analysis: The top SNP for BD susceptibility have been found to be associated with SCZ (and vice versa), as mentioned above and have been reported by others . Additionally, analyses using a polygenic model, such as the polygenic risk profile score (RPS) analysis and genetic correlation analysis, also support the shared genetic risk between the two disorders.…”

Evidence of AS3MTd2d3-Associated Variants within 10q24.32-33 in the Genetic Risk of Major Affective Disorders

“…Among them, 9 studies were excluded because of the overlapped samples and lack of analyses of the SNPs of interest (rs7914558, rs7085104, and rs11191580). Therefore, a total of 5 studies with independent samples were considered eligible for the present meta-analysis [4,5,[11][12][13] . Characteristics of the 5 included samples are listed in Table 1 .…”

“…A total of 3 BPD and 2 MDD studies were included to perform meta-analysis of rs7914558 [4,5,[11][12][13] . Due to the fact that no significant heterogeneity between samples was observed ( p = 0.875, I 2 = 0), a classical fixed effect model was adopted to combine the individual samples.…”

“…A total of three BPD and two MDD studies were included to perform meta-analysis of rs11191580 [4,5,[11][12][13] . A classical fixed effect model was adopted to combine the individual samples since no significant heterogeneity was observed ( p = 0.900, I 2 = 0).…”