抑郁和乳腺癌发病风险相关的孟德尔随机化分析

A Mendelian randomization study of depression and risk of breast cancer

目的:采用两样本孟德尔随机化方法研究抑郁和乳腺癌、结直肠癌、肺癌、卵巢癌、胰腺癌、前列腺癌、皮肤癌发病风险的相关关系。方法:通过自评报告、电子病历和诊断访谈等途径纳入研究对象,从包含三项抑郁全基因组关联研究的meta分析中选择工具变量,用逆方差加权法产生主要结果,具有乘法随机效应的逆方差加权法、加权中值法、MR-Egger法和稳健的调整曲线评分法计算补充结果,评价指标为比值比(OR),进行敏感性分析。结果:利用纳入80万余例的抑郁全基因组关联研究数据和7个癌症数据库,发现抑郁和乳腺癌风险的效应估计值大于1且有统计学意义(OR:1.08;95%CI:1.01~1.17;P=0.035)。结论:抑郁和乳腺癌发病风险可能相关,未发现和其他癌种相关。

Objective:To investi gate the relationships between depression and breast cancer,colorectal canc-er,1ung cancer,pancreatic cancer,prostate cancer,and skin cancer using two-sample Mendelian randomization meth-od.Methods:Participants with self.reported depressive synptoms,hospital admnission records of depression,or structured clinical interview werte included in the original genome wide association studies(GWASs).Single nucle-otide polymorphisms were extacted from GW ASs as instrumental variables.Inverse variance weighted method was utilized to yield main results.Inverse vari ance weighted method with multiplcative random effects,weighted medi-an,MR-Egger method and MR-robust adjusted profile score were utilized to yield supplementary results.Odds ratio(OR)was considered as main result and sensitive tests were conducted Result:Using surnmnary-leve1 data from 1arge-sample GWASs with over more than 800 thousand participants,association of depression with increased breast cancer risk(OR=1.08,95%CI:1.01-1.17,P=0.035)was suggestively found Conclusion:Depression is relat-ed with increased breast cancer risk at suggestive significance leve1,but not with other six types of cancer risk.