Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu 214151, China.
Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu 214151, China.
Schizophr Res. 2024 May;267:528-533. doi: 10.1016/j.schres.2023.09.030. Epub 2023 Sep 19.
The underlying etiology of schizophrenia is still not fully understood, and recent studies have pointed to a potential link between hormonal factors and the risk of developing this condition. Sex Hormone-Binding Globulin (SHBG) is a protein that regulates the bioavailability of sex hormones. However, the causal relationship between SHBG levels and schizophrenia remains unclear, this study aimed to investigate the causal relationship based on two-sample Mendelian randomization (MR) analysis.
This study was based on the summary data of genome-wide association studies (GWAS) of schizophrenia and SHBG in European populations. Two-sample MR was applied, and genetic factors were used as instrumental variables, and the causal relationship between schizophrenia and SHBG was assessed.
We selected 79 single nucleotide polymorphisms with genome-wide significance from the schizophrenia GWAS as instrumental variables. The inverse variance weighting (IVW) method results showed that there is a causal relationship and a positive correlation between schizophrenia and female SHBG, with an odds ratio (OR) of 1.024 (95%CI: 1.007-1.042, P = 0.005), and this result was further confirmed by the Weighted median odds ratio (OR) of 1.032 (95%CI: 1.016-1.048, P = 5.58E-05) and the Weighted mode of 1.035 (95%CI: 1.004-1.067, P = 0.028). Schizophrenia and male SHBG also have a causal relationship and a positive correlation, with an odds ratio (OR) of 1.027 (95%CI: 1.007-1.047, P = 0.008).
This study found a positive correlation between schizophrenia and SHBG in both men and women through MR analysis, indicating that the level of SHBG may be elevated in patients with schizophrenia, regardless of gender.
精神分裂症的潜在病因仍不完全清楚，最近的研究指出激素因素与患这种疾病的风险之间可能存在联系。性激素结合球蛋白（SHBG）是一种调节性激素生物利用度的蛋白质。然而，SHBG 水平与精神分裂症之间的因果关系尚不清楚，本研究旨在通过两样本孟德尔随机化（MR）分析来探讨这种关系。
本研究基于欧洲人群精神分裂症和 SHBG 的全基因组关联研究（GWAS）的汇总数据。应用两样本 MR 分析，将遗传因素作为工具变量，评估精神分裂症与 SHBG 之间的因果关系。
我们从精神分裂症 GWAS 中选择了 79 个具有全基因组意义的单核苷酸多态性作为工具变量。逆方差加权（IVW）法结果表明，精神分裂症与女性 SHBG 之间存在因果关系和正相关，比值比（OR）为 1.024（95%CI：1.007-1.042，P=0.005），这一结果进一步通过加权中位数 OR（OR=1.032，95%CI：1.016-1.048，P=5.58E-05）和加权模式 OR（OR=1.035，95%CI：1.004-1.067，P=0.028）得到证实。精神分裂症与男性 SHBG 之间也存在因果关系和正相关，比值比（OR）为 1.027（95%CI：1.007-1.047，P=0.008）。
本研究通过 MR 分析发现精神分裂症与男女 SHBG 之间呈正相关，表明无论性别如何，精神分裂症患者的 SHBG 水平可能升高。
