The causal relationship between hydatidiform mole and nutrients: A two-sample Mendelian randomization study

Background

Hydatidiform mole (HM), a subset of gestational trophoblastic disease, is considered precancerous and exhibits geographical variation. The incidence of HM is linked to nutritional factors. This study aimed to investigate the causal relationship between nutrients and HM using a bidirectional two-sample Mendelian randomization (MR) approach.

Methods

We utilized publicly available genome-wide association study data to assess the causal associations between levels of specific vitamins (retinol, vitamins B12, B6, C, D, E, folate, and carotene) and minerals (iron, calcium, and magnesium) with HM. The MR analysis was conducted and reported following the STROBE-MR guidelines, employing MR Egger and inverse variance weighted (IVW) methods to estimate associations, with MR-PRESSO for pleiotropy testing.

Results

The study revealed vitamin B6 as a significant protective factor against HM (MR-Egger OR: 0.094, 95 % CI: 0.011–0.0778, P < 0.05; IVW OR: 0.365, 95 % CI: 0.142–0.936, P < 0.05). Folate and magnesium showed suggestive associations with HM, whereas most other nutrients did not exhibit a causal relationship. MR-PRESSO analysis supported the absence of horizontal pleiotropy of vitamin B6. Besides, reverse MR analysis did not reveal a significant causal association between HM and serum nutrient levels, suggesting that differences of nutrients in HM patients may not be directly attributed to the mole.

Conclusion

This MR study provides evidence that vitamin B6 may protect against HM, and suggests potential roles for folate and magnesium in HM development, while highlighting the need for further research to confirm these findings.