Genetically Estimated Ancestry and the Risk of Pre-Eclampsia: A Multiethnic Case-Control Study

Maternal self-reported ethnicity (SRE) is associated with pre-eclampsia (PE) risk and is included in prediction models.

The objectives of the study were to examine whether genetic ancestry estimates are associated with PE and improve the FMF (Fetal Medicine Foundation) PE risk model performance.

PE cases and matched controls from the Harris-Birthright Cohort were genotyped using the Illumina Global Screening Array. Genetic ancestries were estimated using a multiethnic reference panel. African genetic ancestries were incorporated into logistic regression models alongside established clinical risk factors. Area under receiver operating characteristic curves of FMF models with and without genetic ancestries was compared.

This case-control study included 5,207 women: 3,513 White (1,382 PE cases, 2,131 controls) and 1,694 Black SRE (745 PE cases, 949 controls). Ethnicity-ancestry discrepancy was present in 11.3% of self-reporting Black and 5.3% of self-reporting White individuals. Higher West African genetic ancestry was independently associated with increased PE odds. Among self-reporting White women, those with 50% to 100% West African (AFR) ancestry had higher risk vs those with <5% (adjusted OR: 6.46; 95% CI: 3.37 to 12.98; P < 0.001). In self-reporting Black women, lower West AFR ancestry (50% to 84.9%) reduced risk vs those with 85% to 100% (adjusted OR: 0.60; 95% CI: 0.45-0.80; P < 0.001). Incorporating genetic ancestry did not improve FMF model performance.

SRE imperfectly represents genetic ancestry in multiethnic populations. West AFR ancestry independently associates with the PE risk, supporting biological relevance of ancestry-based stratification. However, genetic ancestry did not improve the gold-standard clinical prediction model performance. Large genomic studies in multiethnic cohorts are needed to delineate the genetic architecture of PE.