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

Thorhildur Juliusdottir; Valgerdur Steinthorsdottir; Lilja Stefánsdóttir; 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 Lárus Sigurðsson; Davíð Ottó Arnar; Þóra Steingrímsdóttir; Ingileif Jónsdóttir; Hilma Holm; Daniel F. Gudbjartsson; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Kari Stefansson; Emil L Sigurdsson; David O Arnar; Thora Steingrimsdottir

doi:10.1038/s41588-021-00896-x

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

Thorhildur Juliusdottir, Valgerdur Steinthorsdottir, Lilja Stefánsdóttir, 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 Lárus Sigurðsson, Davíð Ottó Arnar, Þóra Steingrímsdóttir, Ingileif Jónsdóttir, Hilma Holm, Daniel F. Gudbjartsson, Gudmar ThorleifssonUnnur Thorsteinsdottir, Kari Stefansson, Emil L Sigurdsson, David O Arnar, Thora Steingrimsdottir

University of Iceland, Landspitali

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1135-1142
Number of pages	8
Journal	Nature Genetics
Volume	53
Issue number	8
DOIs	https://doi.org/10.1038/s41588-021-00896-x
Publication status	Published - 19 Jul 2021

Bibliographical note

Other keywords

Birth Weight
Fetal Development
Foreldrar
Fæðingarþyngd
Gen
Genome-Wide Association Study

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10.1038/s41588-021-00896-x

https://www.nature.com/articles/s41588-021-00896-x

Cite this

Juliusdottir, T., Steinthorsdottir, V., Stefánsdóttir, L., Sveinbjornsson, G., Ivarsdottir, E. V., Thorolfsdottir, R. B., Sigurdsson, J. K., Tragante, V., Hjorleifsson, K. E., Helgadottir, A., Frigge, M. L., Thorgeirsson, G., Benediktsson, R., Sigurðsson, E. L., Arnar, D. O., Steingrímsdóttir, Þ., Jónsdóttir, I., Holm, H., Gudbjartsson, D. F., ... Steingrimsdottir, T. (2021). Distinction between the effects of parental and fetal genomes on fetal growth. Nature Genetics, 53(8), 1135-1142. https://doi.org/10.1038/s41588-021-00896-x

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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.",

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Juliusdottir, T, Steinthorsdottir, V, Stefánsdóttir, L, Sveinbjornsson, G, Ivarsdottir, EV, Thorolfsdottir, RB, Sigurdsson, JK, Tragante, V, Hjorleifsson, KE, Helgadottir, A, Frigge, ML, Thorgeirsson, G , Benediktsson, R, Sigurðsson, EL, Arnar, DO , Steingrímsdóttir, Þ , Jónsdóttir, I, Holm, H, Gudbjartsson, DF, Thorleifsson, G, Thorsteinsdottir, U, Stefansson, K, Sigurdsson, EL, Arnar, DO & Steingrimsdottir, T 2021, 'Distinction between the effects of parental and fetal genomes on fetal growth', Nature Genetics, vol. 53, no. 8, pp. 1135-1142. https://doi.org/10.1038/s41588-021-00896-x

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T1 - Distinction between the effects of parental and fetal genomes on fetal growth

AU - Juliusdottir, Thorhildur

AU - Steinthorsdottir, Valgerdur

AU - Stefánsdóttir, Lilja

AU - Sveinbjornsson, Gardar

AU - Ivarsdottir, Erna V.

AU - Thorolfsdottir, Rosa B.

AU - Sigurdsson, Jon K.

AU - Tragante, Vinicius

AU - Hjorleifsson, Kristjan E.

AU - Helgadottir, Anna

AU - Frigge, Michael L.

AU - Thorgeirsson, Gudmundur

AU - Benediktsson, Rafn

AU - Sigurðsson, Emil Lárus

AU - Arnar, Davíð Ottó

AU - Steingrímsdóttir, Þóra

AU - Jónsdóttir, Ingileif

AU - Holm, Hilma

AU - Gudbjartsson, Daniel F.

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

AU - Sigurdsson, Emil L

AU - Arnar, David O

AU - Steingrimsdottir, Thora

PY - 2021/7/19

Y1 - 2021/7/19

N2 - 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.

AB - 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.

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KW - Fetal Development

KW - Foreldrar

KW - Fæðingarþyngd

KW - Gen

KW - Genome-Wide Association Study

KW - Birth Weight

KW - Fetal Development

KW - Foreldrar

KW - Fæðingarþyngd

KW - Gen

KW - Genome-Wide Association Study

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DO - 10.1038/s41588-021-00896-x

M3 - Article

C2 - 34282336

SN - 1061-4036

VL - 53

SP - 1135

EP - 1142

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

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

Abstract

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