title: A common variant of HMGA2 is associated with adult and childhood height in the general population.
abstract: Human height is a classic, highly heritable quantitative trait. To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P = 4 x 10(-8)). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P = 3 x 10(-11), overall P = 4 x 10(-16), including the genome-wide association data). We also observed the association in children (P = 1 x 10(-6), N = 6,827) and a tall/short case-control study (P = 4 x 10(-6), N = 3,207). We estimate that rs1042725 explains approximately 0.3% of population variation in height (approximately 0.4 cm increased adult height per C allele). There are few examples of common genetic variants reproducibly associated with human quantitativetraits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height.
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: Guillaume
authors.initials: G
authors.lastname: Lettre
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Freathy
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Voight
authors.forename: John R B
authors.initials: JR
authors.lastname: Perry
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Elliott
authors.forename: Rachel
authors.initials: R
authors.lastname: Hackett
authors.forename: Candace
authors.initials: C
authors.lastname: Guiducci
authors.forename: Beverley
authors.initials: B
authors.lastname: Shields
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.forename: Hana
authors.initials: H
authors.lastname: Lango
authors.forename: Valeriya
authors.initials: V
authors.lastname: Lyssenko
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.forename: Noel P
authors.initials: NP
authors.lastname: Burtt
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Rayner
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.forename: Kristin
authors.initials: K
authors.lastname: Ardlie
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Tobias
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Ness
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Morris
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.forename: Leif C
authors.initials: LC
authors.lastname: Groop
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
mesh_terms: D000328:Adult; D001827:Body Height / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D014644:Genetic Variation; D005838:Genotype; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide
chemical_list: D025743:HMGA2 Protein