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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.

Variability of 128 schizophrenia-associated gene variants across distinct ethnic populations