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Distinction between the effects of parental and fetal genomes on fetal growth
Nature Genetics  (IF38.33),  Pub Date : 2021-07-19, DOI: 10.1038/s41588-021-00896-x
Thorhildur Juliusdottir, Valgerdur Steinthorsdottir, Lilja Stefansdottir, Gardar Sveinbjornsson, Erna V. Ivarsdottir, Rosa B. Thorolfsdottir, Jon K. Sigurdsson, Vinicius Tragante, Kristjan E. Hjorleifsson, Anna Helgadottir, Michael L. Frigge, Gudmundur Thorgeirsson, Rafn Benediktsson, Emil L. Sigurdsson, David O. Arnar, Thora Steingrimsdottir, Ingileif Jonsdottir, Hilma Holm, Daniel F. Gudbjartsson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Kari Stefansson

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.