Ou Zhaoxing, Gao Ziqing, Wang Qi, Lin Yuhong, Ye Dalin
Department of ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
Heliyon. 2023 Sep 27;9(10):e20500. doi: 10.1016/j.heliyon.2023.e20500. eCollection 2023 Oct.
Previous observational research has documented an association between age at first childbirth (AFB) and postpartum depression (PPD). However, the causal relationship remains unclear. This study aimed to assess the causal effects of AFB on PPD using a two-sample Mendelian randomization (MR) analysis.
Three sets of instrumental variables were obtained from the United Kingdom Biobank (UK Biobank), Neale Lab consortium and a meta-analysis of genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with the PPD phenotype were obtained from the Finngen consortium, which included 13,657 cases and 236,178 controls. Inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods to evaluate causal effects. Heterogeneity was assessed using Cochran's Q test and funnel plots. Horizontal pleiotropy and sensitivity were assessed using the MR-Egger intercept test and "leave-one-out" analysis, respectively. Further meta-analysis was performed to validate the robustness of this relationship. Additionally, the potential mediating effects of risk factors associated with PPD were analyzed.
Strong causal effects between AFB and PPD was found in both IVW and weighted median methods, which was further supported by meta-analysis (IVW, odds ratio [OR] 0.59 [95% confidence interval (CI) 0.36-0.96, p = 0.03]; weighted median, OR 0.59 [95% CI 0.37-0.95, p = 0.03]). The power of the MR supports the robustness of the findings. Heterogeneity or horizontal pleiotropy was not observed. Major depressive disorders, family income levels, and marital stress were identified as potential mediating factors in the causal relationships.
Results of MR analysis supported the causal effect of increased AFB in reducing the risk for PPD.
既往观察性研究已记录首次生育年龄（AFB）与产后抑郁症（PPD）之间的关联。然而，因果关系仍不明确。本研究旨在使用两样本孟德尔随机化（MR）分析评估AFB对PPD的因果效应。
从英国生物银行（UK Biobank）、尼尔实验室联盟以及全基因组关联研究（GWAS）的一项荟萃分析中获得了三组工具变量。与PPD表型相关的单核苷酸多态性（SNP）来自芬兰基因联盟，其中包括13657例病例和236178例对照。采用逆方差加权（IVW）、加权中位数、加权众数和MR-Egger方法评估因果效应。使用 Cochr an Q检验和漏斗图评估异质性。分别使用MR-Egger截距检验和“留一法”分析评估水平多效性和敏感性。进行了进一步的荟萃分析以验证这种关系的稳健性。此外，还分析了与PPD相关的危险因素的潜在中介作用。
在IVW和加权中位数方法中均发现AFB与PPD之间存在强因果效应，荟萃分析进一步支持了这一结果（IVW，优势比[OR]为0.59[95%置信区间（CI）为0.36 - 0.96，p = 0.03]；加权中位数，OR为0.59[95%CI为0.37 - 0.95，p = 0.03]）。MR的效能支持了研究结果的稳健性。未观察到异质性或水平多效性。重度抑郁症、家庭收入水平和婚姻压力被确定为因果关系中的潜在中介因素。
MR分析结果支持AFB增加可降低PPD风险的因果效应。
