title: Epigenetic and genetic components of height regulation.
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.
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Stefania
authors.initials: S
authors.lastname: Benonisdottir
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Asmundur
authors.identifier: http://orcid.org/0000-0002-4606-5163
authors.initials: A
authors.lastname: Oddsson
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.|Department of Anthropology, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Agnar
authors.initials: A
authors.lastname: Helgason
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Ragnar P
authors.initials: RP
authors.lastname: Kristjansson
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Gardar
authors.initials: G
authors.lastname: Sveinbjornsson
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Arna
authors.initials: A
authors.lastname: Oskarsdottir
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Olafur B
authors.initials: OB
authors.lastname: Davidsson
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Gudny A
authors.initials: GA
authors.lastname: Arnadottir
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Gerald
authors.initials: G
authors.lastname: Sulem
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Brynjar O
authors.initials: BO
authors.lastname: Jensson
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Hilma
authors.initials: H
authors.lastname: Holm
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Kristjan F
authors.initials: KF
authors.lastname: Alexandersson
authors.affiliation: Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.|Icelandic Cancer Registry, 105 Reykjavik, Iceland.
authors.forename: Laufey
authors.initials: L
authors.lastname: Tryggvadottir
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: G Bragi
authors.identifier: http://orcid.org/0000-0002-5415-6487
authors.initials: GB
authors.lastname: Walters
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Sigurjon A
authors.initials: SA
authors.lastname: Gudjonsson
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Lucas D
authors.initials: LD
authors.lastname: Ward
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Jon K
authors.initials: JK
authors.lastname: Sigurdsson
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.|Reykjavik University, 101 Reykjavik, Iceland.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Iordache
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Michael L
authors.identifier: http://orcid.org/0000-0003-2984-535X
authors.initials: ML
authors.lastname: Frigge
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, 107 Reykjavik, Iceland.
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Gisli
authors.initials: G
authors.lastname: Masson
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, 107 Reykjavik, Iceland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Helgason
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.|School of Engineering and Natural Sciences, University of Iceland, 107 Reykjavik, Iceland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.
authors.forename: Patrick
authors.identifier: http://orcid.org/0000-0001-7123-6123
authors.initials: P
authors.lastname: Sulem
authors.affiliation: deCODE Genetics/Amgen, Inc., 101 Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000328:Adult; D001827:Body Height / Q000235:genetics*; D044127:Epigenesis, Genetic; D056726:Genetic Association Studies; D056426:Genetic Loci; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007055:Iceland; D008957:Models, Genetic