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| 精神障碍可能引起高胆固醇血症:一项孟德尔随机化分析 |
| Mental disorders; Mental illness; hypercholesterolemia; Mendelian randomization; Metabolic disorder syndrome |
| 投稿时间：2024-07-23 修订日期：2025-01-21 |
| DOI： |
| 中文关键词: 精神障碍 高胆固醇血症 孟德尔随机化 代谢障碍综合征 |
| 英文关键词:mental disorders, mental illness, high cholesterol, Mendelian randomization, metabolic disorder syndrome |
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| 中文摘要: |
| 背景 精神障碍患者易出现包括舒张压或收缩压升高、空腹血糖升高和高胆固醇血症、腹型肥胖在内的代谢综合征（MetS）。高胆固醇血症作为MetS的重要组成部分，与精神疾病之间的关系在以往研究中已有讨论与猜想。精神障碍与高胆固醇血症逐年增加的患病率及大量的合并发生，逐渐引发对因果关系及相关机制的系统研究。然而，关于精神障碍本身是否会引起高胆固醇血症，目前尚缺乏全基因组关联研究的支持。目的 本研究通过双样本孟德尔随机化（MR）方法，探究精神障碍与高胆固醇血症之间的潜在因果关联，并检测相关性强度，排除其他混杂因素，证明结果的稳健性。方法 对全基因组关联研究（GWAS）的汇总数据进行分析，使用与暴露因素精神障碍密切相关的单核苷酸多态性（SNP）作为工具变量（IV），以高胆固醇血症为结局变量。分别采用逆方差加权（IVW）、MR-Egger法和加权中位数法（WME法）进行因果分析，以简单众数法（SM）、加权众数法（WM）对结果进行补充，以优势比（OR）评估精神障碍对高胆固醇风险的因果关系。结果 共纳入36个与精神障碍相关的SNP作为IV。以IVW法的结果作为主要结论，结果显示精神障碍与高胆固醇血症之间存在因果关系。每增加1例精神障碍患者，发生高胆固醇血症的风险将升高6.70%（IVW：OR=1.067，95% CI：1.014~1.128，P=0.001）。其余方法（MR-Egger法、WME法、SM法、WM法）结果与IVW方法结果基本一致。进一步验证此结论，未发现精神障碍与高胆固醇血症风险之间的因果关系受遗传多态性的影响（P=0.299）。应用Cochrans’Q统计量和MR-Egger法对IVW法中的异质性进行了计算，结果表明没有显著的异质性（P>0.05）。进一步进行反向因果关联的验证，无明显证据支持高胆固醇血症可引起精神障碍（P>0.05）。结论 精神障碍与高胆固醇血症之间存在因果关系，且精神障碍患者罹患高胆固醇血症的概率可能增加。 |
| 英文摘要: |
| Background Patients with mental disorders are prone to metabolic syndrome (MetS), including elevated diastolic or systolic blood pressure, elevated fasting blood glucose, hypercholesterolemia, and abdominal obesity. As an important component of MetS, the relationship between hypercholesterolemia and mental illness has been discussed and speculated in previous studies. The increasing prevalence of mental disorders and hypercholesterolemia and the large number of co-occurrences have gradually led to systematic studies on causal relationships and related mechanisms. However, there is currently a lack of support from genome-wide association studies on whether mental disorders themselves cause hypercholesterolemia. Objective This study used a two-sample Mendelian randomization (MR) method to explore the potential causal association between mental disorders and hypercholesterolemia, test the strength of the correlation, exclude other confounding factors, and prove the robustness of the results. Methods The summary data of genome-wide association studies (GWAS) were analyzed, and single nucleotide polymorphisms (SNPs) closely associated with exposure factors such as mental disorders were used as instrumental variables (IVs), with hypercholesterolemia as the outcome variable. Causal analysis was performed using inverse variance weighting (IVW), MR-Egger method and weighted median method (WME method), and the results were supplemented by simple mode method (SM) and weighted mode method (WM). The causal relationship between mental disorders and the risk of hypercholesterolemia was evaluated by odds ratio (OR). Results A total of 36 SNPs associated with mental disorders were included as IV. With IVW as the main conclusion, the results showed that there was a causal relationship between mental disorders and hypercholesterolemia. For every additional patient with mental disorder, the risk of hypercholesterolemia would increase by 6.70% (IVW: OR=1.067, 95%CI: 1.014-1.128, P=0.001). The results of other methods (MR-Egger method, WME method, SM method, WM method) were basically consistent with the results of IVW method. Further verification of this conclusion showed that the causal relationship between mental disorders and the risk of hypercholesterolemia was not affected by genetic polymorphism (P=0.299). Cochrans'Q statistic and MR-Egger method were used to calculate the heterogeneity in IVW method, and the results showed that there was no significant heterogeneity (P>0.05). Further verification of reverse causal association showed no obvious evidence to support that hypercholesterolemia can cause mental disorders (P>0.05). Conclusion There is a causal relationship between mental disorders and hypercholesterolemia, and the probability of patients with mental disorders suffering from hypercholesterolemia may be increased. |
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