Chen Chia-Hsiang, Cheng Min-Chih, Hu Tsung-Ming, Ping Lieh-Yung, Kushima Itaru, Aleksic Branko
Department of Psychiatry, Chang Gung Memorial Hospital, Taoyuan.
Department and Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan.
Psychiatr Genet. 2022 Jun 1;32(3):125-130. doi: 10.1097/YPG.0000000000000313. Epub 2022 Mar 31.
Studies showed that rare copy number variations (CNVs) encompassing the vasoactive intestinal peptide receptor 2 gene (VIPR2) were associated with schizophrenia, indicating VIPR2 is a risk gene for schizophrenia. We hypothesized that besides CNV, rare pathogenic single-nucleotide variant (SNV) or small insertion/deletion (Indel) of VIPR2 might be present in some patients and contribute to the pathogenesis of schizophrenia.
We performed genome-wide CNV analysis to screen CNV at the VIPR2 locus and targeted sequencing of all the exons of VIPR2 to search for SNV and indel in a sample of patients with chronic schizophrenia from Taiwan.
We detected a 230-kb microduplication encompassing the VIPR2 in 1 out of 200 patients. Furthermore, we identified six ultrarare SNVs, including one splicing SNV and five missense SNVs, in 516 patients. In-silico analyses showed these SNVs had a damaging effect on the function of VIPR2.
Our findings support the idea that besides CNV, rare pathogenic SNVs of VIPR2 might contribute to the pathogenesis of schizophrenia in some patients.
研究表明，包含血管活性肠肽受体2基因（VIPR2）的罕见拷贝数变异（CNV）与精神分裂症相关，表明VIPR2是精神分裂症的一个风险基因。我们推测，除了CNV外，一些患者中可能存在VIPR2的罕见致病性单核苷酸变异（SNV）或小插入/缺失（Indel），并导致精神分裂症的发病机制。
我们进行了全基因组CNV分析，以筛查VIPR2基因座处的CNV，并对VIPR2的所有外显子进行靶向测序，以在台湾慢性精神分裂症患者样本中寻找SNV和Indel。
我们在200名患者中的1名中检测到一个包含VIPR2的230 kb微重复。此外，我们在516名患者中鉴定出6个超罕见的SNV，包括1个剪接SNV和5个错义SNV。计算机分析表明，这些SNV对VIPR2的功能有损害作用。
我们的研究结果支持这样一种观点，即除了CNV外，VIPR2的罕见致病性SNV可能在一些患者中导致精神分裂症的发病机制。
