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

• Published in: Nature genetics Vol. 53; no. 8; pp. 1135 - 1142
• Main Authors: Juliusdottir, Thorhildur, Steinthorsdottir, Valgerdur, Stefansdottir, Lilja, Sveinbjornsson, Gardar, Ivarsdottir, Erna V., Thorolfsdottir, Rosa B., Sigurdsson, Jon K., Tragante, Vinicius, Hjorleifsson, Kristjan E., Helgadottir, Anna, Frigge, Michael L., Thorgeirsson, Gudmundur, Benediktsson, Rafn, Sigurdsson, Emil L., Arnar, David O., Steingrimsdottir, Thora, Jonsdottir, Ingileif, Holm, Hilma, Gudbjartsson, Daniel F., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2021; Nature Publishing Group
• Subjects: 631/208/205/2138; 692/308/2056; Agriculture; Alleles; Animal Genetics and Genomics; Biomedical and Life Sciences; Biomedicine; Birth size; Birth weight; Blood; Blood pressure; Cancer Research; Consortia; Fetus; Fetuses; Gene Function; Genetic aspects; Genetic research; Genome-wide association studies; Genomes; Genotype; Genotype & phenotype; Gestational age; Growth; Haplotypes; Human Genetics; Insulin; Meta-analysis; Mothers; Parental influences; Physiological aspects; Polygenic inheritance; Ponderal index; Weight reduction; Iceland
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/s41588-021-00896-x

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. Genome-wide association analyses using parental and offspring genotypes provide insights into fetal and maternal genetic effects on fetal growth. The results show that maternal and fetal genomes influence birth weight through distinct mechanisms.