Common maternal and fetal genetic variants show expected polygenic effects on risk of small- or large-for-gestational-age (SGA or LGA), except in the smallest 3% of babies

Beaumont, Robin N.; Wood, A. R.; Knight, Bridget A.; Hattersley, Andrew T.; Freathy, Rachel M.

Common maternal and fetal genetic variants show expected polygenic effects on risk of small- or large-for-gestational-age (SGA or LGA), except in the smallest 3% of babies

Authors

Beaumont, Robin N.

Wood, A. R.

Knight, Bridget A.

Hattersley, Andrew T.

Freathy, Rachel M.

Issue Date

2020-12-07

Type

Journal Article

Language

en

Keywords

Birth Weight , Newborn , Multifactorial Inheritance , Polymorphism , Wessex Classification Subject Headings::Oncology. Pathology.::Genetics

Babies born clinically Small- or Large-for-Gestational-Age (SGA or LGA; sex- and gestational age-adjusted birth weight (BW) <10th or >90th percentile, respectively), are at higher risks of complications. SGA and LGA include babies who have experienced environment-related growth-restriction or overgrowth, respectively, and babies who are heritably small or large. However, the relative proportions within each group are unclear. We assessed the extent to which common genetic variants underlying variation in birth weight influence the probability of being SGA or LGA. We calculated independent fetal and maternal genetic scores (GS) for BW in 11,951 babies and 5,182 mothers. These scores capture the direct fetal and indirect maternal (via intrauterine environment) genetic contributions to BW, respectively. We also calculated maternal fasting glucose (FG) and systolic blood pressure (SBP) GS. We tested associations between each GS and probability of SGA or LGA. For the BW GS, we used simulations to assess evidence of deviation from an expected polygenic model. Higher BW GS were strongly associated with lower odds of SGA and higher odds of LGA (ORfetal = 0.75 (0.71,0.80) and 1.32 (1.26,1.39); ORmaternal = 0.81 (0.75,0.88) and 1.17 (1.09,1.25), respectively per 1 decile higher GS). We found evidence that the smallest 3% of babies had a higher BW GS, on average, than expected from their observed birth weight (assuming an additive polygenic model: Pfetal = 0.014, Pmaternal = 0.062). Higher maternal SBP GS was associated with higher odds of SGA P = 0.005. We conclude that common genetic variants contribute to risk of SGA and LGA, but that additional factors become more important for risk of SGA in the smallest 3% of babies.

Citation

Beaumont RN et al. Common maternal and fetal genetic variants show expected polygenic effects on risk of small- or large-for-gestational-age (SGA or LGA), except in the smallest 3% of babies. PLoS Genet. 2020 Dec 7;16(12):e1009191.

Publisher

Public Library of Science

License

© 2020 Beaumont et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
CC0 1.0 Universal

Journal

PLoS Genetics