Epigenetic and genetic components of height regulation

Stefania Benonisdottir, Asmundur Oddsson, Agnar Helgason, Ragnar P. Kristjansson, Gardar Sveinbjornsson, Arna Oskarsdottir, Gudmar Thorleifsson, Olafur B. Davidsson, Gudny A. Arnadottir, Gerald Sulem, Brynjar O. Jensson, Hilma Holm, Kristjan F. Alexandersson, Laufey Tryggvadottir, G. Bragi Walters, Sigurjon A. Gudjonsson, Lucas D. Ward, Jon K. Sigurdsson, Paul D. Iordache, Michael L. Frigge, Thorunn Rafnar, Augustine Kong, Gisli Masson, Hannes Helgason, Unnur Thorsteinsdottir, Daniel F. Gudbjartsson, Patrick Sulem () and Kari Stefansson ()
Additional contact information
Stefania Benonisdottir: deCODE Genetics/Amgen, Inc.
Asmundur Oddsson: deCODE Genetics/Amgen, Inc.
Agnar Helgason: deCODE Genetics/Amgen, Inc.
Ragnar P. Kristjansson: deCODE Genetics/Amgen, Inc.
Gardar Sveinbjornsson: deCODE Genetics/Amgen, Inc.
Arna Oskarsdottir: deCODE Genetics/Amgen, Inc.
Gudmar Thorleifsson: deCODE Genetics/Amgen, Inc.
Olafur B. Davidsson: deCODE Genetics/Amgen, Inc.
Gudny A. Arnadottir: deCODE Genetics/Amgen, Inc.
Gerald Sulem: deCODE Genetics/Amgen, Inc.
Brynjar O. Jensson: deCODE Genetics/Amgen, Inc.
Hilma Holm: deCODE Genetics/Amgen, Inc.
Kristjan F. Alexandersson: deCODE Genetics/Amgen, Inc.
Laufey Tryggvadottir: Faculty of Medicine, University of Iceland
G. Bragi Walters: deCODE Genetics/Amgen, Inc.
Sigurjon A. Gudjonsson: deCODE Genetics/Amgen, Inc.
Lucas D. Ward: deCODE Genetics/Amgen, Inc.
Jon K. Sigurdsson: deCODE Genetics/Amgen, Inc.
Paul D. Iordache: deCODE Genetics/Amgen, Inc.
Michael L. Frigge: deCODE Genetics/Amgen, Inc.
Thorunn Rafnar: deCODE Genetics/Amgen, Inc.
Augustine Kong: deCODE Genetics/Amgen, Inc.
Gisli Masson: deCODE Genetics/Amgen, Inc.
Hannes Helgason: deCODE Genetics/Amgen, Inc.
Unnur Thorsteinsdottir: deCODE Genetics/Amgen, Inc.
Daniel F. Gudbjartsson: deCODE Genetics/Amgen, Inc.
Patrick Sulem: deCODE Genetics/Amgen, Inc.
Kari Stefansson: deCODE Genetics/Amgen, Inc.

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract Adult height is a highly heritable trait. Here we identified 31.6 million sequence variants by whole-genome sequencing of 8,453 Icelanders and tested them for association with adult height by imputing them into 88,835 Icelanders. Here we discovered 13 novel height associations by testing four different models including parent-of-origin (|β|=0.4–10.6 cm). The minor alleles of three parent-of-origin signals associate with less height only when inherited from the father and are located within imprinted regions (IGF2-H19 and DLK1-MEG3). We also examined the association of these sequence variants in a set of 12,645 Icelanders with birth length measurements. Two of the novel variants, (IGF2-H19 and TET1), show significant association with both adult height and birth length, indicating a role in early growth regulation. Among the parent-of-origin signals, we observed opposing parental effects raising questions about underlying mechanisms. These findings demonstrate that common variations affect human growth by parental imprinting.

Date: 2016
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DOI: 10.1038/ncomms13490

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