Identification of ten loci associated with height highlights new biological pathways in human growth

Guillaume Lettre, Anne U. Jackson, Christian Gieger, Fredrick R. Schumacher, Sonja I. Berndt, Serena Sanna, Susana Eyheramendy, Benjamin F. Voight, Johannah L. Butler, Candace Guiducci, Thomas Illig, Rachel Hackett, Iris M. Heid, Kevin B. Jacobs, Valeriya Lyssenko, Manuela Uda, Michael Boehnke, Stephen J. Chanock, Leif C. Groop, Frank B. HuBo Isomaa, Peter Kraft, Leena Peltonen, Veikko Salomaa, David Schlessinger, David J. Hunter, Richard B. Hayes, Gonçalo R. Abecasis, H. Erich Wichmann, Karen L. Mohlke, Joel N. Hirschhorn

Research output: Contribution to journalArticlepeer-review

Abstract

Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 × 10-7 to 8 × 10-22). Together, these 12 loci account for ∼2% of the population variation in height. Individuals with ≤8 height-increasing alleles and ≥16 height-increasing alleles differ in height by ∼3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait.

Original languageEnglish (US)
Pages (from-to)584-591
Number of pages8
JournalNature genetics
Volume40
Issue number5
DOIs
StatePublished - May 2008

ASJC Scopus subject areas

  • Genetics

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