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A Systematic Review of Mendelian Randomization in Spontaneous Miscarriage
Shiqing Xiang1, Yi Jiang2, Fangxiang Mu3
1Department of Laboratory Diagnosis, Southwest Hospital, Chongqing, 400038, People's Republic of China.
Abstract:
Spontaneous miscarriage (SM) is a common pregnancy complication. Although clinical factors are associated with SM, establishing causality is challenging. Mendelian randomization (MR) helps evaluate the causal effects of exposure variables. This study systematically reviewed 31 MR studies performed in SM, identifying causal relationships between SM and smoking, obesity, insomnia, rheumatoid arthritis, and immune-related factors. Smoking initiation and insomnia were identified as risk factors for SM. Coffee consumption showed no causal association with SM risk. Inconsistent evidence was reported for alcohol intake, BMI, depression, and RA regarding their causal relationships with SM. Smoking initiation, specific cytokines (eg, IL-12, TNF-β), and immune cells (eg, CD4+ T cells) demonstrated causal associations with the number of SM. Notably, key SNPs like rs13261666 and rs7127595 played significant roles in MR analyses due to their strong genetic associations with risk factors. Future research should further investigate the mechanistic pathways linking these genetic variants to SM, aiming to provide precise guidance for clinical prevention and treatment. Additionally, inconsistencies in MR results may stem from differences in data sources, SNP selection criteria, and statistical methodologies, indicating the importance of improving data consistency and standardizing analytical approaches in future research.
Insights
Spontaneous miscarriage (SM) risk is causally linked to smoking initiation and insomnia, according to a systematic review of Mendelian randomization studies. Coffee consumption showed no association, while other factors had inconsistent evidence.
Area of Science:
- Reproductive Health
- Genetics
- Epidemiology
Background:
- Spontaneous miscarriage (SM) is a frequent pregnancy complication with unclear causal factors.
- Mendelian randomization (MR) is a powerful tool for inferring causality from observational data.
Purpose of the Study:
- To systematically review existing MR studies to identify causal risk factors for spontaneous miscarriage.
- To synthesize evidence on the causal relationships between various exposures and SM.
Main Methods:
- Systematic literature search and review of 31 Mendelian randomization studies.
- Analysis of genetic associations between single nucleotide polymorphisms (SNPs) and risk factors for SM.
- Evaluation of causal links between exposures (e.g., smoking, obesity, insomnia) and SM.
Main Results:
- Smoking initiation and insomnia were identified as causal risk factors for SM.
- No causal association was found for coffee consumption.
- Inconsistent evidence existed for alcohol intake, BMI, depression, and rheumatoid arthritis (RA).
- Specific cytokines (IL-12, TNF-β) and immune cells (CD4+ T cells) showed causal links to the number of SM events.
- Key SNPs (rs13261666, rs7127595) were significant in MR analyses.
Conclusions:
- Smoking initiation and insomnia represent modifiable risk factors for spontaneous miscarriage.
- Further research into genetic pathways is needed for targeted prevention and treatment strategies.
- Standardizing MR methodologies and data sources is crucial for consistent findings.
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