BACKGROUND Schizophrenia is a chronic and severe mental disorder, and it has been predicted to be highly polygenic. Common SNPs located in or near BNIP3L were found to be genome-wide significantly associated with schizophrenia in recent genome-wide association studies. The purpose of our study is to investigate potential causal variants in BNIP3L gene. RESULTS We performed targeted sequencing for all exons and un-translated regions of BNIP3L gene among 1806 patients with schizophrenia and 998 healthy controls of Han Chinese origin. Three rare nonsynonymous mutations, BNIP3L (NM_004331): c.52A>G, c.167G>A and c.313A>T, were identified in schizophrenia cases, and two of them were newly reported. The frequencies of these rare nonsynonymous mutations were significantly different between schizophrenia cases and healthy controls. For the common variants, rs147389989 achieved significance in both allelic and genotypic distributions with schizophrenia. Rs1042992 and rs17310286 were significantly associated with schizophrenia in meta-analyses using PGC, CLOZUK, and our new datasets in this study. CONCLUSIONS Our findings provided further evidence that BNIP3L gene is a susceptibility gene of schizophrenia and revealed functional and potential causal mutations in BNIP3L. However, more functional validations are suggested to better understand the role of BNIP3L in the etiology of schizophrenia.

中文翻译：

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鉴定BNIP3L中的罕见和常见变体：精神分裂症易感基因。

背景技术精神分裂症是一种慢性和严重的精神疾病，并且据预测是高度多基因的。在最近的全基因组关联研究中，发现位于BNIP3L或附近的常见SNP与精神分裂症显着相关。我们研究的目的是研究BNIP3L基因中潜在的因果变异。结果我们对1806例精神分裂症患者和998例汉族健康对照者的BNIP3L基因的所有外显子和非翻译区域进行了靶向测序。在精神分裂症患者中鉴定出三个罕见的非同义突变BNIP3L（NM_004331）：c.52A> G，c.167G> A和c.313A> T，其中两个新报道。这些罕见的非同义突变的频率在精神分裂症患者和健康对照者之间显着不同。对于常见变体，rs147389989在精神分裂症的等位基因和基因型分布中均具有重要意义。使用PGC，CLOZUK和本研究中的新数据集进行荟萃分析时，Rs1042992和rs17310286与精神分裂症显着相关。结论我们的发现提供了进一步的证据，表明BNIP3L基因是精神分裂症的易感基因，并且揭示了BNIP3L中的功能性和潜在因果突变。但是，建议进行更多的功能验证，以更好地了解BNIP3L在精神分裂症病因中的作用。结论我们的发现提供了进一步的证据，表明BNIP3L基因是精神分裂症的易感基因，并且揭示了BNIP3L中的功能性和潜在因果突变。但是，建议进行更多的功能验证，以更好地了解BNIP3L在精神分裂症病因中的作用。结论我们的发现提供了进一步的证据，表明BNIP3L基因是精神分裂症的易感基因，并且揭示了BNIP3L中的功能性和潜在因果突变。但是，建议进行更多的功能验证，以更好地了解BNIP3L在精神分裂症病因中的作用。