Institute of Mental Health, Hainan Provincial Anning Hospital, No 10, Nanhai Avenue East, Haikou, 571100, Hainan, China.
First Department of Psychiatry, Hainan Provincial Anning Hospital, Haikou, 571100, Hainan, China.
BMC Med Genomics. 2021 Sep 4;14(1):218. doi: 10.1186/s12920-021-01070-2.
Schizophrenia (SCZ) is a severe mental illness with high heritability. This study aimed to explore the correlation between MAD1L1, TSNARE polymorphisms and SCZ susceptibility.
A total of 493 SCZ patients and 493 healthy controls were included. The genotypes of MAD1L1 and TSNARE polymorphisms were identified by Agena MassARRAY platform. Odds ratio (OR) and 95% confidence intervals (CIs) were tested via logistic regression analysis in multiple genetic models and different subgroups.
We observed that AG genotype of rs1107592, AG genotype of rs4976976, and CA genotype of rs67756423 decreased the susceptibility to SCZ (p < 0.05). Age stratification analysis showed that the TC genotype of rs12666575, AG genotype of rs1107592, and AG genotype of rs4976976 decreased the risk of SCZ individuals older than 36 years (p < 0.05). In addition, the AG and AA genotype of rs4976976, the CA genotype of rs67756423 were associated with a lower risk of SCZ in males (p < 0.05). In females, the TT genotype of rs12666575 in recessive model, the AG and AA-AG genotype of rs1107592 in heterozygote and dominant model, could reduce the susceptibility to SCZ (p < 0.05). However, no significant association was found after Bonferroni correction.
Our results suggest that MAD1L1 and TSNARE genetic polymorphisms exert a protective role in the risk of SCZ. These findings provide evidence that MAD1L1 and TSNARE may serve as potential biomarkers of SCZ. However, a replication experiment in a cohort with large sample size are required to confirm our findings. Trial registration Not applicable.
精神分裂症（SCZ）是一种具有高遗传性的严重精神疾病。本研究旨在探讨 MAD1L1、TSNARE 多态性与 SCZ 易感性的相关性。
共纳入 493 例 SCZ 患者和 493 例健康对照者。采用 Agena MassARRAY 平台检测 MAD1L1 和 TSNARE 多态性的基因型。采用多因素遗传模型和不同亚组的逻辑回归分析检测比值比（OR）和 95%置信区间（CI）。
我们发现 rs1107592 的 AG 基因型、rs4976976 的 AG 基因型和 rs67756423 的 CA 基因型降低了 SCZ 的易感性（p<0.05）。年龄分层分析表明，rs12666575 的 TC 基因型、rs1107592 的 AG 基因型和 rs4976976 的 AG 基因型降低了 36 岁以上 SCZ 个体的发病风险（p<0.05）。此外，rs4976976 的 AG 和 AA 基因型、rs67756423 的 CA 基因型与男性 SCZ 的发病风险较低相关（p<0.05）。在女性中，rs12666575 的隐性模型 TT 基因型、rs1107592 的杂合子和显性模型 AG 和 AA-AG 基因型可降低 SCZ 的易感性（p<0.05）。然而，经过 Bonferroni 校正后，没有发现显著的相关性。
我们的结果表明，MAD1L1 和 TSNARE 遗传多态性对 SCZ 的风险具有保护作用。这些发现为 MAD1L1 和 TSNARE 可能作为 SCZ 的潜在生物标志物提供了证据。然而，需要在一个具有大样本量的队列中进行重复实验来验证我们的发现。
