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

• Published in: Nature genetics Vol. 40; no. 5; pp. 584 - 591
• Main Authors: Lettre, Guillaume, Jackson, Anne U, Gieger, Christian, Schumacher, Fredrick R, Berndt, Sonja I, Sanna, Serena, Eyheramendy, Susana, Voight, Benjamin F, Butler, Johannah L, Guiducci, Candace, Illig, Thomas, Hackett, Rachel, Heid, Iris M, Jacobs, Kevin B, Lyssenko, Valeriya, Uda, Manuela, Boehnke, Michael, Chanock, Stephen J, Groop, Leif C, Hu, Frank B, Isomaa, Bo, Kraft, Peter, Peltonen, Leena, Salomaa, Veikko, Schlessinger, David, Hunter, David J, Hayes, Richard B, Abecasis, Gonçalo R, Wichmann, H-Erich, Mohlke, Karen L, Hirschhorn, Joel N
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.05.2008; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedical research; Biomedicine; Body Height - genetics; Cancer; Cancer Research; Chromatin remodeling; Clinical Medicine; Diabetes; Endocrinology and Diabetes; Endokrinologi och diabetes; Fundamental and applied biological sciences. Psychology; Gene Function; Gene loci; Genetic aspects; Genetic factors; Genetic Linkage; Genetic variation; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Hedgehog protein; Height; Human Genetics; Humans; Identification and classification; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Meta-analysis; Physical growth; Physiological aspects; Polygenic inheritance; Polymorphism, Single Nucleotide; Quantitative trait loci; Reviews; Sample size; Signal transduction; Single-nucleotide polymorphism; Stature; Studies; United States; Human; Identification; Locus; Growth
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.125

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.