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, Xuemin; Liu, Linfei

doi:10.3389/fpsyt.2024.1287934

Cited by 2 publications

(1 citation statement)

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“…The standard Inverse Variance Weighted (IVW) method (a random-effects model) ( 11 ) is the primary evaluative approach for investigating the causal relationship between metabolites and Major Depressive Disorder (MDD) in this analysis, encompassing both forward and reverse MR analyses. MR-Egger and the Weighted Median (WM) provide secondary methods of evaluation.…”

Section: Methodsmentioning

confidence: 99%

Assessing the associations of 1,400 blood metabolites with major depressive disorder: a Mendelian randomization study

Dong,

Wang,

Jia

et al. 2024

Front. Psychiatry

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Background and objectivesMajor Depressive Disorder (MDD) is one of the most prevalent and debilitating health conditions worldwide. Previous studies have reported a link between metabolic dysregulation and MDD. However, evidence for a causal relationship between blood metabolites and MDD is lacking.MethodsUsing a two-sample bidirectional Mendelian randomization analysis (MR), we assessed the causal relationship between 1,400 serum metabolites and Major Depressive Disorder (MDD). The Inverse Variance Weighted method (IVW) was employed to estimate the causal association between exposures and outcomes. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode methods were used as supplementary approaches for a comprehensive appraisal of the causality between blood metabolites and MDD. Pleiotropy and heterogeneity tests were also conducted. Lastly, the relevant metabolites were subjected to metabolite function analysis, and a reverse MR was implemented to explore the potential influence of MDD on these metabolites.ResultsAfter rigorous screening, we identified 34 known metabolites, 13 unknown metabolites, and 18 metabolite ratios associated with Major Depressive Disorder (MDD). Among all metabolites, 33 were found to have positive associations, and 32 had negative associations. The top five metabolites that increased the risk of MDD were the Arachidonate (20:4n6) to linoleate (18:2n6) ratio, LysoPE(18:0/0:0), N-acetyl-beta-alanine levels, Arachidonate (20:4n6) to oleate to vaccenate (18:1) ratio, Glutaminylglutamine, and Threonine to pyruvate ratio. Conversely, the top five metabolites that decreased the risk of MDD were N6-Acetyl-L-lysine, Oleoyl-linoleoyl-glycerol (18:1 to 18:2) [2] to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] ratio, Methionine to phosphate ratio, Pregnanediol 3-O-glucuronide, and 6-Oxopiperidine-2-carboxylic acid. Metabolite function enrichment was primarily concentrated in pathways such as Bile Acid Biosynthesis (FDR=0.177), Glutathione Metabolism (FDR=0.177), Threonine, and 2-Oxobutanoate Degradation (FDR=0.177). In addition, enrichment was noted in pathways like Valine, Leucine, and Isoleucine Biosynthesis (p=0.04), as well as Ascorbate and Aldarate Metabolism (p=0.04).DiscussionWithin a pool of 1,400 blood metabolites, we identified 34 known metabolites and 13 unknown metabolites, as well as 18 metabolite ratios associated with Major Depressive Disorder (MDD). Additionally, three functionally enriched groups and two metabolic pathways were selected. The integration of genomics and metabolomics has provided significant insights for the screening and prevention of MDD.

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Section: Methodsmentioning

confidence: 99%

Assessing the associations of 1,400 blood metabolites with major depressive disorder: a Mendelian randomization study

Dong,

Wang,

Jia

et al. 2024

Front. Psychiatry

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Causal effect of the age at first birth with depression: a mendelian randomization study

Guo,

Song

et al. 2024

BMC Med Genomics

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Background This study aimed to explore the causal relationship between age at first birth (AFB) and depression. Methods Using the univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) methods to examine the potential correlation between age at first birth (AFB) and major depressive disorder and postpartum depression. A public database was used to obtain the genome-wide association studies (GWAS) summary data. We put inverse-variance-weighted (IVW) as the primary method in Mendelian randomization (MR) analysis and used sensitivity analysis to confirm the robustness of our result. Results We found a significant causal association between AFB and major depressive disorder by using the IVW algorithm (odd ratio [OR] 0.826; 95% confidence interval [CI] 0.793 − 0.861; P = 4.51 × 10− 20). MR-Egger, weighted median, simple mode and weighted mode method concluded the same result (P < 0.05). During the sensitivity analysis, the heterogeneity test (Q-value = 55.061, df = 48, P = 2.81 × 10− 01, I2 = 12.82%) and the leave-one-out plot analysis confirmed the stability of the results. The outcomes of the pleiotropy test (MR-Egger intercept = 8.932 × 10− 3. SE = 6.909 × 10− 3. P = 2.02 × 10− 01) and MR_PRESSO global test (P = 2.03 × 10− 01) indicated there is no pleiotropy. Conclusion There is solid evidence that a higher age at first birth is associated with a lower risk of major depressive disorder.

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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

Cited by 2 publications

References 42 publications

Assessing the associations of 1,400 blood metabolites with major depressive disorder: a Mendelian randomization study

Assessing the associations of 1,400 blood metabolites with major depressive disorder: a Mendelian randomization study

Causal effect of the age at first birth with depression: a mendelian randomization study

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