title: Identification of ten loci associated with height highlights new biological pathways in human growth.
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.
authors.affiliation: Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lettre
authors.forename: Anne U
authors.initials: AU
authors.lastname: Jackson
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.forename: Susana
authors.initials: S
authors.lastname: Eyheramendy
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Voight
authors.forename: Johannah L
authors.initials: JL
authors.lastname: Butler
authors.forename: Candace
authors.initials: C
authors.lastname: Guiducci
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Rachel
authors.initials: R
authors.lastname: Hackett
authors.forename: Iris M
authors.initials: IM
authors.lastname: Heid
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Jacobs
authors.forename: Valeriya
authors.initials: V
authors.lastname: Lyssenko
authors.forename: Manuela
authors.initials: M
authors.lastname: Uda
authors.forename: Michael
authors.initials: M
authors.lastname: Boehnke
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Leif C
authors.initials: LC
authors.lastname: Groop
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Bo
authors.initials: B
authors.lastname: Isomaa
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
mesh_terms: D001827:Body Height / Q000235:genetics*; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D020641:Polymorphism, Single Nucleotide