Abstract
Schizophrenia is a common polygenetic disease affecting 0.5–1% of individuals across distinct ethnic populations. PGC-II, the largest genome-wide association study investigating genetic risk factors for schizophrenia, previously identified 128 independent schizophrenia-associated genetic variants (GVs). The current study examined the genetic variability of GVs across ethnic populations. To assess the genetic variability across populations, the 'variability indices' (VIs) of the 128 schizophrenia-associated GVs were calculated. We used 2504 genomes from the 1000 Genomes Project taken from 26 worldwide healthy samples comprising five major ethnicities: East Asian (EAS: n=504), European (EUR: n=503), African (AFR: n=661), American (AMR: n=347) and South Asian (SAS: n=489). The GV with the lowest variability was rs36068923 (VI=1.07). The minor allele frequencies (MAFs) were 0.189, 0.192, 0.256, 0.183 and 0.194 for EAS, EUR, AFR, AMR and SAS, respectively. The GV with the highest variability was rs7432375 (VI=9.46). The MAFs were 0.791, 0.435, 0.041, 0.594 and 0.508 for EAS, EUR, AFR, AMR and SAS, respectively. When we focused on the EAS and EUR population, the allele frequencies of 86 GVs significantly differed between the EAS and EUR (P<3.91 × 10−4). The GV with the highest variability was rs4330281 (P=1.55 × 10−138). The MAFs were 0.023 and 0.519 for the EAS and EUR, respectively. The GV with the lowest variability was rs2332700 (P=9.80 × 10−1). The MAFs were similar between these populations (that is, 0.246 and 0.247 for the EAS and EUR, respectively). Interestingly, the mean allele frequencies of the GVs did not significantly differ between these populations (P>0.05). Although genetic heterogeneities were observed in the schizophrenia-associated GVs across ethnic groups, the combination of these GVs might increase the risk of schizophrenia.
Highlights
Schizophrenia is a common, complex psychiatric disease with a lifetime prevalence of ~ 0.5–1%1,2 and an estimated heritability of ~ 80%.3 The incidence of schizophrenia is uniform worldwide.[1,4,5] Hundreds of common genetic variants (GVs) have been weakly implicated in the pathogenesis of schizophrenia.[6,7] Genome-wide association studies (GWASs), which examine millions of GVs, are powerful tools for identifying common susceptibility variants associated with complex disorders across diverse populations
We focused on the genetic variability of the schizophreniaassociated variants between the East Asian (EAS) and EUR populations utilized in our first analysis because these groups represented the major ethnicities that participated in a previous GWAS.[7]
To the best of our knowledge, this study is the first to examine the genetic variability of the 128 linkage disequilibrium (LD)-independent recalculated the variability indices' (VIs) of the schizophrenia-associated GVs in the remaining four populations
Summary
Schizophrenia is a common, complex psychiatric disease with a lifetime prevalence of ~ 0.5–1%1,2 and an estimated heritability of ~ 80%.3 The incidence of schizophrenia is uniform worldwide.[1,4,5] Hundreds of common genetic variants (GVs) have been weakly implicated in the pathogenesis of schizophrenia.[6,7] Genome-wide association studies (GWASs), which examine millions of GVs, are powerful tools for identifying common susceptibility variants associated with complex disorders (including schizophrenia) across diverse populations. The incidence of schizophrenia is uniform worldwide.[1,4,5] Hundreds of common genetic variants (GVs) have been weakly implicated in the pathogenesis of schizophrenia.[6,7] Genome-wide association studies (GWASs), which examine millions of GVs, are powerful tools for identifying common susceptibility variants associated with complex disorders (including schizophrenia) across diverse populations. The largest GWAS in the Schizophrenia Working Group of the Psychiatric Genomics Consortium (GWAS PGC-II), including 36 989 patients with schizophrenia and 113 075 controls, has identified 128 linkage disequilibrium (LD)-independent variants across 108 genomic loci.[7] most of these participants were of European (EUR) ancestry. The second most common ethnic population included case–control samples from East Asia (1866 cases and 3418 controls)
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