Causal association between plasma vascular endothelial growth factor family proteins and placenta previa: A 2-sample Mendelian randomization study.
5 affiliations
- 1Department of Blood Transfusion, Foshan Maternal and Child Health Hospital, Foshan, China.
- 2Department of Organ Transplantation, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
- 3Department of Blood Transfusion, The Second People's Hospital of Foshan, Foshan, China.
- 4Department of Blood Transfusion, Jiangmen Central Hospital, Jiangmen, China.
- 5Department of Blood Transfusion, Foshan First People's Hospital, Foshan, China.
Abstract
This study investigates associations between genetically proxied plasma vascular endothelial growth factor (VEGF) family proteins and placenta previa using 2-sample Mendelian randomization (MR). Exposure GWAS summary statistics were obtained from the UK Biobank and IEU resources, and placenta previa data from FinnGen. Inverse-variance weighted (IVW) analysis was the primary method, supplemented by MR-Egger, weighted median, and weighted mode analyses. The Bonferroni-corrected threshold for 5 exposures was P < .01. Cochran Q, the MR-Egger intercept, MR-PRESSO and leave-one-out analyses assessed heterogeneity and sensitivity. Genetically predicted higher plasma VEGFA was associated with increased placenta previa risk (IVW: β = 0.231, OR = 1.26, 95% confidence interval: 1.06-1.51, P = .008). The analyses did not provide statistically convincing evidence of a causal effect of VEGFB, VEGFC, VEGFD, or placental growth factor (PLGF); these findings should not be interpreted as evidence of no effect. For VEGFA specifically, Cochran Q test did not detect significant heterogeneity (IVW: Q = 21.257, P = .729), and the MR-Egger intercept (-0.026, P = .181) and MR-PRESSO global test (P = .692) did not detect evidence of horizontal pleiotropy. The VEGFA leave-one-out analysis indicated that no single SNP substantially influenced the estimate. In contrast, VEGFD showed a significant MR-Egger intercept (-0.155, P = .029), indicating possible directional horizontal pleiotropy and requiring particular caution in interpreting this exposure. The findings support an association between genetically proxied plasma VEGFA and placenta previa risk. They provide etiologic insight rather than evidence of clinical prediction; any predictive or screening role for VEGFA measurement requires prospective, pregnancy-specific validation.
Related
- The association between inflammation and pubertal development : Insights from NHANES and Mendelian randomization analyses
- Causal relationship between oral microbiome, circulating inflammatory proteins and lung cancer: A Mendelian randomization study.
- The causal association between Celiac disease and Ankylosing spondylitis: a two-sample Mendelian randomization analysis.
- Association between ankylosing spondylitis and hearing loss: A Mendelian randomization study.
- Association of 14 matrix metalloproteinases and 4 tissue inhibitors of metalloproteinases on ankylosing spondylitis : A bidirectional Mendelian randomization study
BibTeX
@article{hong2026causal,
title = {{Causal association between plasma vascular endothelial growth factor family proteins and placenta previa: A 2-sample Mendelian randomization study.}},
author = {Zhantong Hong and Zhibin Xu and Zeqi Huang and Weichao Li and Qifeng Liu},
journal = {Medicine},
year = {2026},
month = oct,
doi = {10.1097/md.0000000000051193},
url = {https://europepmc.org/article/MED/42888602},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Causal association between plasma vascular endothelial growth factor family proteins and placenta previa: A 2-sample Mendelian randomization study.
AU - Zhantong Hong
AU - Zhibin Xu
AU - Zeqi Huang
AU - Weichao Li
AU - Qifeng Liu
PY - 2026
DA - 2026/10/01
JO - Medicine
DO - 10.1097/md.0000000000051193
UR - https://europepmc.org/article/MED/42888602
AB - This study investigates associations between genetically proxied plasma vascular endothelial growth factor (VEGF) family proteins and placenta previa using 2-sample Mendelian randomization (MR). Exposure GWAS summary statistics were obtained from the UK Biobank and IEU resources, and placenta previa data from FinnGen. Inverse-variance weighted (IVW) analysis was the primary method, supplemented by MR-Egger, weighted median, and weighted mode analyses. The Bonferroni-corrected threshold for 5 exposures was P < .01. Cochran Q, the MR-Egger intercept, MR-PRESSO and leave-one-out analyses assessed heterogeneity and sensitivity. Genetically predicted higher plasma VEGFA was associated with increased placenta previa risk (IVW: β = 0.231, OR = 1.26, 95% confidence interval: 1.06-1.51, P = .008). The analyses did not provide statistically convincing evidence of a causal effect of VEGFB, VEGFC, VEGFD, or placental growth factor (PLGF); these findings should not be interpreted as evidence of no effect. For VEGFA specifically, Cochran Q test did not detect significant heterogeneity (IVW: Q = 21.257, P = .729), and the MR-Egger intercept (-0.026, P = .181) and MR-PRESSO global test (P = .692) did not detect evidence of horizontal pleiotropy. The VEGFA leave-one-out analysis indicated that no single SNP substantially influenced the estimate. In contrast, VEGFD showed a significant MR-Egger intercept (-0.155, P = .029), indicating possible directional horizontal pleiotropy and requiring particular caution in interpreting this exposure. The findings support an association between genetically proxied plasma VEGFA and placenta previa risk. They provide etiologic insight rather than evidence of clinical prediction; any predictive or screening role for VEGFA measurement requires prospective, pregnancy-specific validation.
SN - 0304-5412
SN - 1536-5964
ER -