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

  • Nat Genet. 2008 May;40(5):584-91. doi: 10.1038/ng.125.
Guillaume Lettre  1 ,  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 ,  Diabetes Genetics Initiative ,  FUSION ,  KORA ,  Prostate, Lung Colorectal and Ovarian Cancer Screening Trial ,  Nurses' Health Study ,  SardiNIA ,  Michael Boehnke ,  Stephen J Chanock ,  Leif C Groop ,  Frank B Hu ,  Bo 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
Affiliations
  • 1. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
PMID: 18391950 DOI: 10.1038/ng.125
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 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 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.