title: Genome-wide association analysis identifies 20 loci that influence adult height.
abstract: Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.
authors.affiliation: Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Weedon
authors.forename: Hana
authors.initials: H
authors.lastname: Lango
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.forename: Chris
authors.initials: C
authors.lastname: Wallace
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Freathy
authors.forename: John R B
authors.initials: JR
authors.lastname: Perry
authors.forename: Suzanne
authors.initials: S
authors.lastname: Stevens
authors.forename: Alistair S
authors.initials: AS
authors.lastname: Hall
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Beverly
authors.initials: B
authors.lastname: Shields
authors.forename: Inga
authors.initials: I
authors.lastname: Prokopenko
authors.forename: Martin
authors.initials: M
authors.lastname: Farrall
authors.forename: Anna
authors.initials: A
authors.lastname: Dominiczak
authors.forename: Toby
authors.initials: T
authors.lastname: Johnson
authors.forename: Sven
authors.initials: S
authors.lastname: Bergmann
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Waterworth
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Morris
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.forename: Jing Hua
authors.initials: JH
authors.lastname: Zhao
authors.forename: Shengxu
authors.initials: S
authors.lastname: Li
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.forename: Inês
authors.initials: I
authors.lastname: Barroso
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Deloukas
authors.forename: Manjinder S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: Eleanor
authors.initials: E
authors.lastname: Wheeler
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Mark
authors.initials: M
authors.lastname: Caulfield
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Munroe
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
mesh_terms: D000328:Adult; D000368:Aged; D001827:Body Height / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D005838:Genotype; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D016326:Extracellular Matrix Proteins; D053823:Hedgehog Proteins; D009363:Neoplasm Proteins