Li Xin-Wei, Zhang Ming-Yuan, Li Zhi-Jun, Ai Li-Zhe, Jin Meng-Di, Jia Ning-Ning, Xie Meng-Tong, Yang Yu-Qing, Li Wei-Zhen, Dong Lin, Yu Qiong
Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China.
Department of Endemic Diseases and Parasitic Diseases Prevention, Yantai Center for Disease Control and Prevention, Yantai 264003, Shandong Province, China.
World J Psychiatry. 2022 Jul 19;12(7):904-914. doi: 10.5498/wjp.v12.i7.904.
Schizophrenia (SCZ) is a complex disease which can be affected by both genetic and environmental factors. Prenatal famine exposure may cause changes in DNA methylation levels of genes. Meanwhile, maternal nutrition during pregnancy is a pivotal environmental factor in the development of SCZ. DNA methylation may be an intermediate factor mediating exposure to famine during pregnancy and SCZ, and DNA methylation quantitative trait loci might serve as a promising tool for linking SCZ and prenatal famine.
To analyze the association between prenatal famine exposure and SCZ risk in Northeast Han Chinese through analysis of DNA methylation related loci.
A total of 954 Han Chinese from Northeast China were recruited, including 443 patients with SCZ and 511 healthy controls. The participants were further divided into famine (born in 1960-1962) and non-famine (born in 1963-1965) groups to investigate the effect of prenatal famine exposure. Four single-nucleotide polymorphisms (SNPs) selected according to the relevant literature were genotyped, namely, rs11917047 in , rs2239681 in , rs3842756 in and rs61955196 in . DNA were extracted from peripheral blood samples, and the genotypes of these SNP loci were detected using the improved Multiple Ligase Detection Reaction multiple SNP typing technique. The associations of the DNA methylation related SNPs with SCZ risk and prenatal famine, and their interactions were analyzed using logistic regression analysis and generalized multifactor dimensionality reduction (GMDR) software.
Based on the sequencing data, genotype distributions and allele frequencies of the four selected SNPs were determined. All genotype frequencies of the four SNPs in the healthy control group were tested for deviation from Hardy-Weinberg equilibrium ( > 0.05). Logistic regression analysis showed that rs61955196 was significantly associated with SCZ risk in the log-additive model [odds ratio (OR): 1.22; 95% confidence interval (CI): 1.01-1.48; = 0.040]. We also found that the rs61955196 allele was related with an enhanced risk of SCZ (G>C, OR: 1.22; 95%CI: 1.01-1.47; = 0.042). However, no associations were observed between rs11917047, rs2239681, or rs3842756 and SCZ risk. Under the optimal genetic model, no significant association of famine with the four SNPs was seen. Though the gene-gene interactions between rs2239681 and rs61955196 were found in GMDR analysis, none of the gene-gene interactions and gene-famine interactions were associated with the risk of SCZ.
Our study suggested that rs61955196 in is associated with SCZ susceptibility in Northeast Han Chinese, providing insight into genetic effects on SCZ.
精神分裂症（SCZ）是一种复杂疾病，受遗传和环境因素共同影响。产前饥荒暴露可能导致基因DNA甲基化水平发生变化。同时，孕期母亲营养是SCZ发病过程中的一个关键环境因素。DNA甲基化可能是介导孕期饥荒暴露与SCZ之间关系的一个中间因素，而DNA甲基化数量性状位点可能是连接SCZ与产前饥荒的一个有前景的工具。
通过分析DNA甲基化相关位点，探讨东北汉族人群产前饥荒暴露与SCZ风险之间的关联。
共纳入954名来自中国东北的汉族人，其中443例SCZ患者和511名健康对照。参与者进一步分为饥荒组（出生于1960 - 1962年）和非饥荒组（出生于1963 - 1965年），以研究产前饥荒暴露的影响。根据相关文献选择4个单核苷酸多态性（SNP）进行基因分型，分别为位于[具体位置未给出]的rs11917047、位于[具体位置未给出]的rs2239681、位于[具体位置未给出]的rs3842756和位于[具体位置未给出]的rs61955196。从外周血样本中提取DNA，采用改进的多重连接酶检测反应多重SNP分型技术检测这些SNP位点的基因型。使用逻辑回归分析和广义多因素降维（GMDR）软件分析DNA甲基化相关SNP与SCZ风险、产前饥荒之间的关联及其相互作用。
根据测序数据，确定了4个选定SNP的基因型分布和等位基因频率。对健康对照组中4个SNP的所有基因型频率进行哈迪 - 温伯格平衡检验（P>0.05）。逻辑回归分析显示，在对数加性模型中，rs61955196与SCZ风险显著相关[比值比（OR）：1.22；95%置信区间（CI）：1.01 - 1.48；P = 0.040]。我们还发现rs61955196等位基因与SCZ风险增加相关（G>C，OR：1.22；95%CI：1.01 - 1.47；P = 0.042）。然而，未观察到rs11917047、rs2239681或rs3842756与SCZ风险之间存在关联。在最优遗传模型下，未发现饥荒与这4个SNP之间存在显著关联。尽管在GMDR分析中发现rs2239681与rs61955196之间存在基因 - 基因相互作用，但基因 - 基因相互作用和基因 - 饥荒相互作用均与SCZ风险无关。
我们的研究表明，位于[具体位置未给出]的rs61955196与东北汉族人群的SCZ易感性相关，为了解基因对SCZ的影响提供了依据。
