Journal Article

Epigenetic and genetic components of height regulation

Oddsson, Asmundur, Sulem, Gerald, Masson, Gisli, Thorleifsson, Gudmar, Frigge, Michael L., Sveinbjornsson, Gardar, Thorsteinsdottir, Unnur, Kristjansson, Ragnar P., Davidsson, Olafur B., Rafnar, Thorunn, Holm, Hilma, Sigurdsson, Jon K., Kong, Augustine, Benonisdottir, Stefania, Gudbjartsson, Daniel F., Jensson, Brynjar O., Helgason, Agnar, Stefansson, Kari, Walters, G. Bragi, Sulem, Patrick, Helgason, Hannes, Arnadottir, Gudny A., Tryggvadottir, Laufey, Iordache, Paul D., Gudjonsson, Sigurjon A., Oskarsdottir, Arna, Alexandersson, Kristjan F., Ward, Lucas D.

2016

Overview

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. Adult height has a strong genetic component and is highly heritable. Here the authors whole-genome sequence 8,453 Icelanders and find novel parent-of-origin derived associations in IGF2-H19 and DLK1-MEG3 .

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/91 / 631/208/176/1968 / 631/208/205/2138 / Adult / Birth / Body height / Body Height - genetics / Epigenesis, Genetic / Epigenetics / Gene expression / Gene sequencing / Genetic Association Studies / Genetic Loci / Genetic Variation / Genomes / Genotype / Growth factors / Humanities and Social Sciences / Humans / Iceland / Imprinting / Insulin-like growth factor II / Models, Genetic / multidisciplinary / Nucleotide sequence / Preadipocyte factor 1 / Science / Science (multidisciplinary)