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Pregnancy hypertension
Published

Association of genetic ancestry with pre-eclampsia in multi-ethnic cohorts of pregnant women

Authors

Frances Conti-Ramsden, Antonio de Marvao, Carolyn Gill, Lucy C Chappell, Jenny Myers, Dragana Vuckovic, Abbas Dehghan, Pirro G Hysi

Abstract

Pregnancy Hypertens. 2024 Oct 4;38:101162. doi: 10.1016/j.preghy.2024.101162. Online ahead of print.

ABSTRACT

OBJECTIVES: Maternal self-reported ethnicity is recognised as a risk factor for pre-eclampsia in clinical screening tools and models. This study investigated whether ethnicity is acting as a proxy for genetic variants in this context.

STUDY DESIGN: A total of 436 women from multi-ethnic backgrounds recruited to two UK observational pregnancy hypertension cohort studies were genotyped. Genetically-computed individual ancestry estimates were calculated for each individual through comparison to the multi-ethnic 1000 Genomes reference panel genotypes. Regression models for pre-eclampsia using clinical risk factors including self-reported ethnicity with and without ancestry estimates were built and compared using Likelihood Ratio Tests (LRT).

MAIN OUTCOME MEASURES: Pre-eclampsia (early- and late-onset).

RESULTS: In these multi-ethnic cohorts (mean age 34.9 years; 41.3 % White, 34.2 % Black, 13.1 % Asian ethnic backgrounds; 82.6 % chronic hypertension), discrepancies between self-reported ethnicity and genetically-computed individual ancestry estimates were present in all ethnic groups, particularly minority groups. Genetically-computed pan-African ancestry percentage was associated with early-onset (< 34 weeks) pre-eclampsia in adjusted models (aOR 100 % vs 0 % African ancestry: 3.81, 95 % CI 1.04-14.14, p-value 0.044) independently of self-reported ethnicity and established clinical risk factors. Addition of genetically-computed African ancestry to a clinical risk factor model including self-reported ethnicity, improved model fit (Likelihood ratio test p-value 0.023).

CONCLUSIONS: Self-reported maternal ethnicity is an imperfect proxy for genetically-computed individual ancestry estimates, particularly in ethnic minority groups. Genetically-computed African ancestry percentage was associated with early-onset pre-eclampsia independently of self-reported maternal ethnicity. Well-powered studies in multi-ethnic cohorts are required to delineate the genetic contribution to pre-eclampsia.

PMID:39368288 | DOI:10.1016/j.preghy.2024.101162

UK DRI Authors

Abbas Dehghan

Prof Abbas Dehghan

Professor in Molecular Epidemiology, School of Public Health, Faculty of Medicine, Imperial College London

Prof Abbas Dehghan