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

TY - JOUR

T1 - Association of genetic ancestry with pre-eclampsia in multi-ethnic cohorts of pregnant women

AU - Conti-Ramsden, Frances

AU - de Marvao, Antonio

AU - Gill, Carolyn

AU - Chappell, Lucy C.

AU - Myers, Jenny

AU - Vuckovic, Dragana

AU - Dehghan, Abbas

AU - Hysi, Pirro G.

N1 - Publisher Copyright: © 2024 The Authors

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

KW - Ancestry

KW - Ethnicity

KW - Pre-eclampsia

KW - Pregnancy

UR - http://www.scopus.com/inward/record.url?scp=85205596427&partnerID=8YFLogxK

U2 - 10.1016/j.preghy.2024.101162

DO - 10.1016/j.preghy.2024.101162

M3 - Article

AN - SCOPUS:85205596427

SN - 2210-7789

VL - 38

JO - Pregnancy Hypertension

JF - Pregnancy Hypertension

M1 - 101162

ER -