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Generalisability of Maternal Genetic Risk Score for Birth Weight Across Racial Identity and Ancestry: A Secondary Analysis of a Prospective Cohort Study

Title: Generalisability of Maternal Genetic Risk Score for Birth Weight Across Racial Identity and Ancestry: A Secondary Analysis of a Prospective Cohort Study
Authors: Tristani-Firouzi, Bita; Pappas, Lisa; Joseph, Merry; Zeinomar, Maryam; Debbink, Michelle P.; Mims, Joseph; Guerrero, Rafael; Moore, Barry; Silver, Robert M.; Workalemahu, Tsegaselassie; Haas, David; Steller, Jonathan G.; Saade, George; Blue, Nathan R.
Contributors: Obstetrics and Gynecology, School of Medicine
Source: PMC
Publisher Information: Wiley
Publication Year: 2026
Collection: Indiana University - Purdue University Indianapolis: IUPUI Scholar Works
Subject Terms: Equity; Foetal growth; Genetic risk score; Polygenic risk score
Description: Objective: Maternal genotypes may be useful to customise foetal growth assessment, but generalisability across diverse racial and ancestral groups remains uncertain. We assessed the generalisability of a genetic risk score for birth weight (GRSBW), derived from participants of predominantly European ancestry, within a diverse U.S. Design: Secondary analysis of a prospective observational cohort of nulliparous patients. Setting: Eight U.S. recruitment centers. Population or sample: Participants in the parent study with available maternal DNA. Methods: We used log-linear modelling to test the association of maternal GRSBW with infant birth weight. We then assessed the robustness of the association by self-identified race and genetically predicted continental ancestry (GPA) groups. Main outcome measures: Birth weight. Results: Among 8147 eligible participants, GRSBW was positively associated with birth weight (p < 0.001). Across self-identified racial groups, the association was significant in White (n = 5394, mean ratio 1.04, 95% CI 0.97-1.11, p = 0.007) and multiracial (n = 508, mean ratio 1.10, CI 1.01-1.2, p = 0.03) groups but not in Black (n = 1139), Asian (n = 358), or unknown race groups (p > 0.09 for all). Among GPA groups, the association was significant among European (mean ratio 1.04, CI 1.02-1.07, p = 0.001) and American (mean ratio 1.08, CI 1.01-1.14, p = 0.02) ancestry groups but not African, East or South Asian, or unknown ancestry (p > 0.05 for all). Conclusions: This GRSBW is not generalisable across self-described racial identities or GPA groups, highlighting the need for globally representative genetic discovery cohorts as well as further investigation into the complex role of race, ethnicity, and epigenetic influences on foetal growth.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: BJOG; https://hdl.handle.net/1805/54454
Availability: https://hdl.handle.net/1805/54454
Rights: Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.B0256E2E
Database: BASE