Women's reproductive traits and major depressive disorder: A two-sample Mendelian randomization study

Wang, Zhenqian; Lu, Jiawen; Weng, Weipin; Fu, Jianhan; Zhang, Jie

doi:10.1016/j.jad.2023.01.063

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…Stillbirth increases the risk of PPD up to thrice when compared to live birth [19] . Our study indicates that AMC, AMP, and PPD are not genetically causally related, whereas previous studies have suggested that both are associated with an increased risk of depression [48,49] . It might be as a result of the genetic variations between PPD and MDD.…”

Section: Discussioncontrasting

confidence: 81%

Causal relationship between Women's reproductive traits and postpartum depression: a multivariate Mendelian randomization analysis

Kang,

Wu,

Cao

et al. 2023

Preprint

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Background: The relationship between women's reproductive traits and postpartum depression (PPD) has not been clarified. We reveal the association between genetically predicted modifiable women’s reproductive traits and PPD using two-sample Mendelian randomization (MR). Methods: We used genome-wide association studies (GWASs) to obtain instrumental variables (IVs) of 10 women's reproductive traits. Univariate and multivariate MR analyses were used to examine the association between traits and the risk of PPD (13,657 cases and 236,178 controls). The primary causal effect assessment employed IVW method. Results: In the UVMR result, genetic prediction showed that age at first sexual intercourse (AFS) (OR = 0.474, 95% CI 0.396-0.567; P = 4.6×10-16), age at first birth (AFB) (OR = 0.865, 95% CI 0.805-0.930; P = 8.02×10-5), and age at last live birth (ALLB) (OR = 0.296, 95% CI 0.138-0.636; P = 0.002) were significantly inversely associated with PPD, while a higher lifetime number of sexual partners (LNSP) (OR = 1.431, 95% CI 1.009-2.031; P = 0.045) and a greater number of spontaneous miscarriages (OR = 1.519, 95% CI 1.021-2.262; P = 0.039) are suggested associated with an increased risk of PPD. In the MVMR result, only AFB (OR = 0.804, 95% CI 0.661-0.978; P = 0.029) and spontaneous abortion (OR = 1.182; 1.036-1.348; P = 0.013) retained a direct causative relationship with PPD. Conclusions: We confirmed that AFB and spontaneous abortion are high-risk factors for PPD. Our findings further support revising the diagnostic criteria (ICD-10) such that PPD is independent of major depressive disorder.

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Section: Discussioncontrasting

confidence: 81%

Causal relationship between Women's reproductive traits and postpartum depression: a multivariate Mendelian randomization analysis

Kang,

Wu,

Cao

et al. 2023

Preprint

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“…Previous MR studies have shown that both early AFS and early AFB are risk factors for major depressive disorder (MDD) ( 24 , 25 ). Most studies, including control groups of nonperinatal women, have concluded that PPD differs from nonperinatal depression in women ( 26 , 27 ).…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization analyses for the causal relationship between early age at first sexual intercourse, early age at first live birth, and postpartum depression in pregnant women

Zhao,

Liu

2024

Front. Psychiatry

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IntroductionThere are insufficient epidemiological studies on the impact of age at first sexual intercourse (AFS) and age at first live birth (AFB) on postpartum depression (PPD) in pregnant women, and the conclusions of these studies are inconsistent.MethodsWe performed a Mendelian randomization (MR) study to determine the causal relationship between AFS or AFB and the risk of PPD. The summary data were extracted from genome-wide association study (GWAS) summary datasets. We selected the instrumental variables according to the P value of exposure-related single nucleotide polymorphisms (P<5 ×10-9 for AFS and P<5 ×10-8 for AFB) and estimated the linkage disequilibrium using the clump parameter (10,000 kb, r2 < 0.001). Single nucleotide polymorphisms were considered instrumental variables that were significantly associated with exposure factors without linkage disequilibrium. The F-statistics of the instrumental variables should all be larger than 10. A random-effects model of IVW was constructed as the main method in our study.Results and discussionMR studies based on GWAS data revealed that both AFS (OR = 0.4, P <0.001) and AFB (OR = 0.38, P <0.001) were negatively correlated with the risk of PPD. Early AFS and early AFB should be studied as possible risk factors for PPD in the future. Public health departments should attach importance to sex education for young girls. The results of our TSMR should be verified by high-quality prospective epidemiological studies in the future.

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“…[ 21 ] The heterogeneity was detected, and the randomized-effects IVW model was applied; otherwise, the fixed-effects model was used. [ 22 ] The weighted median method was used as a supplementary method for at least 50% of the analysis weights from inverse variance (IV). [ 23 ] If all SNPs were ineffective tools, then the MR–Egger method was used.…”

Section: Methodsmentioning

confidence: 99%

Causal analysis of gastroesophageal reflux disease and esophageal cancer

Wang,

Li,

Zhou

et al. 2024

Medicine

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Patients with gastroesophageal reflux disease (GERD) are more likely to develop esophageal cancer (EC). However, a causal relationship between the 2 has been difficult to determine. Therefore, this study aimed to evaluate the impact of GERD on EC using the Mendelian randomization (MR) method. The causal association between GERD and EC was analyzed based on 2 publicly available genetic summary datasets for the GERD cohort (129,080 cases vs 473,524 controls) and the EC cohort (740 cases vs 372,016 controls). The causal inference was mainly evaluated by the inverse variance weighted MR. The MR-Egger regression, MR Pleiotropy Residual Sum and Outlier test, and leave-one-out test were used to confirm the sensitivity of the MR results. Possible interfering factors were excluded by multivariate MR (MVMR) analysis. We used 73 single nucleotide polymorphisms as instrumental variables. GERD was associated with increasing EC risk (odds ratio [OR], 1.001; 95% confidence interval, 1.001–1.002; P < .001), which was identified using the inverse variance weighted method. The sensitivity analysis also demonstrated similar results with the causal explanation, and major bias in genetic pleiotropy was not identified (intercept, 0.001; standard error, 0.001; P = .418). The multivariate MR analysis demonstrated the effect of GERD on EC even after excluding possible mediating factors (OR, 1.003; 95% confidence interval, 1.001–1.005; P = .012). This study confirmed that GERD has a causal effect on EC. Therefore, interventional measures are recommended to prevent EC.

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Women's reproductive traits and major depressive disorder: A two-sample Mendelian randomization study

Cited by 10 publications

References 39 publications

Causal relationship between Women's reproductive traits and postpartum depression: a multivariate Mendelian randomization analysis

Causal relationship between Women's reproductive traits and postpartum depression: a multivariate Mendelian randomization analysis

Mendelian randomization analyses for the causal relationship between early age at first sexual intercourse, early age at first live birth, and postpartum depression in pregnant women

Causal analysis of gastroesophageal reflux disease and esophageal cancer

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