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Nat Genet DOI:10.1038/ng.125

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

Publication TypeJournal Article
Year of Publication2008
AuthorsLettre, G, Jackson, AU, Gieger, C, Schumacher, FR, Berndt, SI, Sanna, S, Eyheramendy, S, Voight, BF, Butler, JL, Guiducci, C, Illig, T, Hackett, R, Heid, IM, Jacobs, KB, Lyssenko, V, Uda, M, Boehnke, M, Chanock, SJ, Groop, LC, Hu, FB, Isomaa, B, Kraft, P, Peltonen, L, Salomaa, V, Schlessinger, D, Hunter, DJ, Hayes, RB, Abecasis, GR, Wichmann, H-E, Mohlke, KL, Hirschhorn, JN
Corporate AuthorsDiabetes Genetics Initiative, FUSION, KORA, Prostate, Lung Colorectal and Ovarian Cancer Screening Trial, Nurses' Health Study, SardiNIA
JournalNat Genet
Volume40
Issue5
Pages584-91
Date Published2008 May
ISSN1546-1718
KeywordsBody Height, Genetic Linkage, Genome, Human, Humans, Polymorphism, Single Nucleotide
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 =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.

URLhttp://dx.doi.org/10.1038/ng.125
DOI10.1038/ng.125
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/18391950?dopt=Abstract

Alternate JournalNat. Genet.
PubMed ID18391950
PubMed Central IDPMC2687076
Grant List5 R01 DK 075787 / DK / NIDDK NIH HHS / United States
R56 DK062370 / DK / NIDDK NIH HHS / United States
U01 HL084729 / HL / NHLBI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
R01 HG002651 / HG / NHGRI NIH HHS / United States
5U01CA098233 / CA / NCI NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
CA49449 / CA / NCI NIH HHS / United States
R01 DK062370 / DK / NIDDK NIH HHS / United States
HL084729 / HL / NHLBI NIH HHS / United States
/ / Intramural NIH HHS / United States
DK62370 / DK / NIDDK NIH HHS / United States
U01 CA098233 / CA / NCI NIH HHS / United States
5P01CA087969 / CA / NCI NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
HG02651 / HG / NHGRI NIH HHS / United States
089061 / / Wellcome Trust / United Kingdom
R01 CA049449 / CA / NCI NIH HHS / United States
U01 CA049449 / CA / NCI NIH HHS / United States
DK72193 / DK / NIDDK NIH HHS / United States