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精神分裂症与乳腺癌之间关联的孟德尔随机化研究
作者:唐伟1  徐向楠2  符德元2 
单位:1. 大连医科大学 扬州临床医学院, 辽宁 大连 116044;
2. 苏北人民医院 甲乳外科, 江苏 扬州 225001
关键词:精神分裂症 乳腺癌 孟德尔随机化 
分类号:R737.9; R749.3
出版年·卷·期(页码):2024·52·第一期(96-101)
摘要:

目的:应用两样本孟德尔随机化研究评估精神分裂症和乳腺癌风险之间的因果关系。方法:从公开的全基因组关联研究(GWAS)的汇总统计数据库提取精神分裂症和乳腺癌数据,将与精神分裂症有关的单核苷酸多态性(SNP)作为工具变量,使用逆方差加权法、MR-Egger回归、加权中位数法等进行孟德尔双样本随机化评估两者之间的因果关系。以比值比(OR)及95%CI评估结果。使用漏斗图、Cochrans Q检验和MR-Egger截距检验等进一步验证结果的一致性。结果:总共提取了68个SNPs为工具变量,逆方差加权法得出精神分裂症和乳腺癌的OR值为1.043,95%CI 1.016~1.070,且差异具有统计学意义(P=0.002)。加权中位数法、MR-Egger法、简单众数法和加权众数法同样得出了相似的结果。多效性检测未发现明显水平多效性(P=0.242)。留一法分析得出没有工具变量会对结果产生强烈影响,该因果关系是正向的。结论:本研究得出了精神分裂症和乳腺癌存在因果关系,即精神分裂症会增加乳腺癌的发生风险,这可能为在精神分裂症患者中进行额外的乳腺癌筛查提供了指导。

Objective: This study employed two-sample Mendelian randomization to evaluate the causal relationship between schizophrenia and the risk of developing breast cancer. Methods: Data on schizophrenia and breast cancer were obtained from publicly available summary statistics databases of genome-wide association studies(GWAS). Single nucleotide polymorphisms(SNPs) associated with schizophrenia were utilized as instrumental variables to assess the causal relationship between schizophrenia and breast cancer. This evaluation was performed using methods such as inverse variance-weighted, MR-Egger regression, and weighted median in a two-sample Mendelian randomization.Odds ratio(OR) and 95%confidence interval(CI) were used to evaluate the results. The consistency of the results was further evaluated using funnel plots, Cochran's Q test, and MR-Egger intercept test. Results: A total of 68 SNPs were extracted as instrumental variables. The inverse variance-weighted method yielded an OR of 1.043 95%CI 1.016~1.070 for the association between schizophrenia and breast cancer, with a statistically significant(P=0.002). Similar results were obtained using the weighted median approach, MR-Egger method, simple mode method, and weighted mode method. No evidence of substantial heterogeneity was found through heterogeneity testing(P=0.242). Leave-one-out analysis indicated that no single instrumental variable strongly influenced the results, supporting a positive causal relationship. Conclusion: This study presents evidence supporting a causal link between schizophrenia and breast cancer, indicating that individuals with schizophrenia may have an elevated risk of developing breast cancer. These findings have implications for guiding the implementation of additional breast cancer screening in patients with schizophrenia.

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