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Published August 2021 | Supplemental Material
Journal Article Open

Distinction between the effects of parental and fetal genomes on fetal growth

Abstract

Birth weight is a common measure of fetal growth that is associated with a range of health outcomes. It is directly affected by the fetal genome and indirectly by the maternal genome. We performed genome-wide association studies on birth weight in the genomes of the child and parents and further analyzed birth length and ponderal index, yielding a total of 243 fetal growth variants. We clustered those variants based on the effects of transmitted and nontransmitted alleles on birth weight. Out of 141 clustered variants, 22 were consistent with parent-of-origin-specific effects. We further used haplotype-specific polygenic risk scores to directly test the relationship between adult traits and birth weight. Our results indicate that the maternal genome contributes to increased birth weight through blood-glucose-raising alleles while blood-pressure-raising alleles reduce birth weight largely through the fetal genome.

Additional Information

© 2021 Nature Publishing Group. Received 16 December 2020; Accepted 11 June 2021; Published 19 July 2021. We thank the participants of this study and the investigators of the FinnGen study. Part of this work was conducted using the UKBB resource (application no. 56270). Data availability: The GWAS summary statistics from this study have been deposited at deCODE genetics (https://www.decode.com/summarydata/). Publicly available datasets used in this study were EGG Consortium datasets: http://mccarthy.well.ox.ac.uk/publications/2019/EggBirthWeight_NatureGenetics/Fetal_BW_European_meta.NG2019.txt.gz, http://mccarthy.well.ox.ac.uk/publications/2019/EggBirthWeight_NatureGenetics/Maternal_BW_European_meta.NG2019.txt.gz and https://egg-consortium.org/downloads/EGG-GWAS-BL.txt.gz. Other data generated or analyzed during this study are included in this article and Supplementary Tables 1–12. Code availability: Custom code has been uploaded to the following GitHub repository: https://github.com/birthw/code. These authors contributed equally: Thorhildur Juliusdottir, Valgerdur Steinthorsdottir. Author Contributions: T.J., V.S., H.H., D.F.G., G. Thorleifsson, U.T. and K.S. designed the study and interpreted the results. V.S., A.H., G. Thorgeirsson, R.B., E.L.S., D.O.A., T.S. and I.J. carried out participant ascertainment and recruitment. T.J., V.S., L.S., G.S., E.V.I., R.B.T., J.K.S., V.T., K.E.H., M.L.F., D.F.G. and G. Thorleifsson performed the statistical and bioinformatics analyses. T.J., V.S., U.T. and K.S. drafted the manuscript. All authors contributed to the final version of the manuscript. Competing interests: T.J., V.S., L.S., G.S., E.V.I., R.B.T., J.K.S., V.T., K.E.H., A.H., M.L.F., G. Thorgeirsson, D.O.A., I.J., H.H., D.F.G., G. Thorleifsson, U.T. and K.S. are affiliated with deCODE Genetics/Amgen and declare competing interests as employees. The other authors declare no competing interests. Peer review information: Nature Genetics thanks Rachel Freathy and David Evans for their contribution to the peer review of this work.

Attached Files

Supplemental Material - 41588_2021_896_Fig10_ESM.webp

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Supplemental Material - 41588_2021_896_MOESM4_ESM.xlsx

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Additional details

Created:
August 22, 2023
Modified:
October 23, 2023