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


Autoři: Robin N. Beaumont aff001;  Sarah J. Kotecha aff002;  Andrew R. Wood aff001;  Bridget A. Knight aff001;  Sylvain Sebert aff003;  Mark I. McCarthy aff005;  Andrew T. Hattersley aff001;  Marjo-Riitta Jarvelin aff003;  Nicholas J. Timpson aff010;  Rachel M. Freathy aff001;  Sailesh Kotecha aff002
Působiště autorů: Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, United Kingdom aff001;  Department of Child Health, School of Medicine, Cardiff University, Cardiff, United Kingdom aff002;  Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulun yliopisto, Finland aff003;  Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland aff004;  Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom aff005;  Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom aff006;  Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom aff007;  Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom aff008;  Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Kingston Lane, Uxbridge, Middlesex, United Kingdom aff009;  Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom aff010
Vyšlo v časopise: 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 16(12): e1009191. doi:10.1371/journal.pgen.1009191
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009191

Souhrn

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.

Klíčová slova:

Birth – Birth weight – Genetic polymorphism – Genetics – Genome-wide association studies – Medical risk factors – Metaanalysis – Single nucleotide polymorphisms


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PLOS Genetics


2020 Číslo 12

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