Causal Effect of Age at Menarche on the Risk for Depression: Results From a Two-Sample Multivariable Mendelian Randomization Study

Hirtz, Raphael; Hars, Christine; Naaresh, Roaa; Laabs, Björn‐Hergen; Antel, Jochen; Grasemann, Corinna; Peters, Triinu

doi:10.3389/fgene.2022.918584

Cited by 15 publications

(19 citation statements)

References 92 publications

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“…Thus, adverse outcomes regarding mental health conferred by the genotype underlying pubertal timing might be counterbalanced by advantageous effects related to the same set of genes and their individual allelic architecture in males but not in females. This would explain the findings of the present study as well as the observation of adverse effects of earlier pubertal timing in girls on the mental health phenotype (Hirtz et al, 2022).…”

Section: Closely Related But Yet Distinct -Pubertal Timing In Girls A...supporting

confidence: 75%

“…However, for valid conclusions of the MR, the genetic architecture of depression should not change throughout the life course. As previously discussed in more detail (Hirtz et al, 2022), a recent genome-wide association meta-analysis showed that the genetic architecture of . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.…”

Section: Male Pubertal Timing and Mddmentioning

confidence: 74%

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No Relationship between Male Pubertal Timing and Depression – New Insights from Epidemiology and Mendelian Randomization

Hirtz

Grasemann

Hoelling

et al. 2023

Preprint

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BackgroundIn males, the relationship between pubertal timing and depression is understudied and less consistent than in females, likely for reasons of unmeasured confounding. To clarify this relationship, a combined epidemiological and genetic approach was chosen to exploit the methodological advantages of both approaches.MethodsData from 2,026 males from a nationwide study (KiGGS) were used to investigate the non-/linear relationship between pubertal timing defined by the age at voice break and major depressive disorder (MDD), considering a multitude of potential confounders and their interactions with pubertal timing. This analysis was complemented by Mendelian Randomization (MR), which is robust to inferential problems inherent to epidemiological studies. We used 71 single nucleotide polymorphisms related to pubertal timing in males as instrumental variable to clarify its causal relationship with MDD based on data from 807,553 individuals (246,363 cases and 561,190 controls) by univariable and multivariable MR, including BMI as pleiotropic phenotype.ResultsUnivariable MR indicated a causal effect of pubertal timing on MDD risk (inverse-variance weighted: OR=0.93, 95%-CI [0.87–0.99)], p=.03). However, this was not confirmed by multivariable MR (inverse-variance weighted: OR=0.95, 95%-CI [0.88–1.02)], p=.13), consistent with the epidemiological approach (OR=1.01, 95%-CI [0.81–1.26], p=.93). Instead, the multivariable MR study indicated a causal relationship of BMI with MDD by two of three methods.ConclusionsPubertal timing is not related to MDD risk in males. Considering the adverse health outcomes of higher BMI levels, our findings support the rationale for preventive measures to address obesity and its related risk factors.

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Section: Closely Related But Yet Distinct -Pubertal Timing In Girls A...supporting

confidence: 75%

Section: Male Pubertal Timing and Mddmentioning

confidence: 74%

No Relationship between Male Pubertal Timing and Depression – New Insights from Epidemiology and Mendelian Randomization

Hirtz

Grasemann

Hoelling

et al. 2023

Preprint

Self Cite

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“…Years of schooling were converted and standardized, where each unit represented 4.2 years of schooling (1 standard deviation [SD] = 4.2 years). Based on published MR studies ( 17 , 18 ), a total of 268 single nucleotide polymorphisms (SNPs) were selected in our study for MR analysis ( Supplementary Table 2 ). According to previous studies, these SNPs accounted for 12% of the variation in EA among individuals ( 16 ).…”

Section: Methodsmentioning

confidence: 99%

Causal effects of education attainment on oral and oropharyngeal cancer: New evidence from a meta-analysis and Mendelian randomization study

Chen

Xie

Liu

et al. 2023

Front. Public Health

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ObjectivesHigher educational attainment (EA) has proven to be beneficial for preventing and treating various types of cancers. Currently, there is little evidence on the association between EA and prevention of oral cavity and pharyngeal cancer (OCPC).MethodsSeveral databases were searched until October 1, 2022, and a meta-analysis was performed. A Mendelian randomization (MR) study was conducted with EA (i.e., the exposure) data derived from the Social Science Genetic Association Consortium and 6,034 cases of OCPC (i.e., outcome) selected from the Integrative Epidemiology Unit genome-wide association study. Five methods were used to evaluate the causality between EA and OCPC. The leave-one-out sensitivity test, MR-Egger regression, and multivariable MR (MVMR) analysis were applied to evaluate the MR results.ResultsThe meta-analysis included 36 eligible studies. EA was significantly and negatively associated with OCPC risk (odds ratio [OR]: 0.439, 95% confidence interval [CI]: 0.383–0.503, P < 0.001). MR analysis revealed that the risk of OCPC, oropharyngeal cancer, and oral cavity cancer decreased with an increase in education (OR: 0.349, 95% CI: 0.222–0.548, P < 0.001; OR: 0.343, 95% CI: 0.198–0.597; P < 0.001; OR: 0.342, 95% CI: 0.195–0.601, P < 0.001, respectively). Even after correcting for mediators, high EA still significantly reduced the risk of OCPC (OR: 0.361, 95% CI: 0.281–0.463, P < 0.001).ConclusionBoth the meta-analysis and MR results demonstrated that high levels of EA can reduce the risk of OCPC in the general population.

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“…Mental health has been linked to certain reproductive behaviors (RB) and socioeconomic status (SES) (7) (8) (9).Postpartum depression, being a mental disorder associated with childbirth, is susceptible to being in uenced by women's reproductive behaviors. To date, various studies have found that early age at menarche and menopause, as well as early age at rst intercourse, are linked with an increased risk of depression (10) (11) (12).…”

Section: Introductionmentioning

confidence: 99%

Reproductive behaviors, socioeconomic status and risk for postpartum depression: A Mendelian randomization study

Han

Feng

2023

Preprint

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Background There is a growing body of evidence showing an association between women's reproductive behavior (RB) and socio-economic status (SES) with the incidence of postpartum depression (PPD). However, the causal relationship between these factors and PPD remains unclear. To facilitate timely screening and effective prevention of maternal emotional disorders, we conducted a Mendelian randomization (MR) study to assess causality between RB/SES and PPD. This study aims to provide new insights into the etiology of PPD and inform public health strategies for its prevention and management. Methods A two-sample Mendelian randomization (MR) study was conducted to investigate the causal effects of reproductive behavior (RB) and socio-economic status (SES) on postpartum depression (PPD). Strongly associated genetic variants for each phenotype were selected as instrumental variables using a predetermined threshold. The primary analysis was conducted using inverse variance weighted method, with additional MR methods including MR-Egger, weighted median, and weighted mode estimate. Potential pleiotropy of instrumental variables (IVs) was evaluated using the MR pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression methods, and outliers were identified by MR-PRESSO. Heterogeneity among IVs was assessed using Cochran's Q statistic. Leave-one-out sensitivity analysis was performed to identify SNPs that significantly impacted the results. This study aims to provide a better understanding of the causal relationship between RB/SES and PPD and inform future prevention and intervention strategies. Result We found a statistically significant association between age of first sexual intercourse , age at first birth, lifetime number of sexual partners, age completed full-time education, Townsend deprivation index at recruitment, and PPD. However, after Bonferroni correction, only earlier age of first sexual intercourse and age completed full-time education remained significantly associated with an increased risk of PPD. These results were reliable and stable and sensitivity analysis showed no violation of the MR assumptions. This study provides important insights into the causal relationship between RB and SES on PPD and highlights the need for targeted interventions to address risk factors for PPD. Conclusions. MR study provides robust evidence that SES/RB play broad impacts on PPD.

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Causal Effect of Age at Menarche on the Risk for Depression: Results From a Two-Sample Multivariable Mendelian Randomization Study

Cited by 15 publications

References 92 publications

No Relationship between Male Pubertal Timing and Depression – New Insights from Epidemiology and Mendelian Randomization

No Relationship between Male Pubertal Timing and Depression – New Insights from Epidemiology and Mendelian Randomization

Causal effects of education attainment on oral and oropharyngeal cancer: New evidence from a meta-analysis and Mendelian randomization study

Reproductive behaviors, socioeconomic status and risk for postpartum depression: A Mendelian randomization study

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