SynthesisEuropean journal of clinical nutrition2022
Homocysteine and female fertility, pregnancy loss and offspring birthweight: a two-sample Mendelian randomization study.
Synthesis in European journal of clinical nutrition, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review.European journal of epidemiology · 2024Pooled it
- Maternal hyperhomocysteinemia compromises female offspring fertility through overactivation of primordial follicles.iScience · 2026Article
- Dysregulated homocysteine metabolism and cardiovascular disease and clinical treatments.Molecular and cellular biochemistry · 2025Review
- A Systematic Review of Mendelian Randomization in Spontaneous Miscarriage.Journal of multidisciplinary healthcare · 2025Review
- Associations between 25 hydroxyvitamin D concentration and spontaneous abortion.BMC public health · 2024Article
- Recent Advances in Folates and Autoantibodies against Folate Receptors in Early Pregnancy and Miscarriage.Nutrients · 2023Review
- Homocysteine-Potential Novel Diagnostic Indicator of Health and Disease in Horses.Animals : an open access journal from MDPI · 2023Review
- Review of mendelian randomization studies on age at natural menopause.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
objectivesObservational studies link elevated homocysteine concentrations (Hcy) with female fertility, pregnancy loss, and low offspring birthweight. Maternal rs1801133, a functional variant in MTHFR strongly associated with lifelong elevated Hcy, is associated with recurrent pregnancy loss and offspring birthweight in Asian women. We investigated if genetically elevated Hcy is associated with fertility, pregnancy loss, and offspring birthweight in European women. SUBJECTS/
methodsWe performed a two-sample Mendelian randomization (MR) study using publicly available data. We obtained 18 genetic variants (five involved in Hcy metabolism) explaining up to 5.9% of the variance in Hcy from a genome-wide association meta-analysis of 44,147 European individuals (82% women). We investigated fertility (including age at menopause), pregnancy loss, and offspring birthweight in the UK Biobank (N = 194,174), EGG (N = 190,406), and ReproGen (N = 69,360-252,514) consortia using summary statistics. We calculated inverse-variance weighted, and several sensitivity MR regression statistics.
resultsrs1801133 was associated with a 7.45 months (95% CI: 4.09, 10.80) increase in age at menopause and 29.69 (12.87, 46.51) g decrease in offspring birthweight per SD increase in Hcy in the UK biobank, and confirmed in EGG and ReproGen. MR for Hcy metabolism alone (five variants in MTHFR, MTR, CBS) showed similar results for offspring birthweight across consortia. However, using all 18 variants resulted in no association for any of the outcomes across consortia.
conclusionHcy and suggestively vitamin B variants are most likely the drug targets for folate supplementation in pregnant women on the offspring birthweight, while Hcy variants related to renal function or diabetes are not involved.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.