A common variant of HMGA2 is associated with adult and childhood height in the general population.
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.
Weedon
Michael N
MN
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK.
Lettre
Guillaume
G
Freathy
Rachel M
RM
Lindgren
Cecilia M
CM
Voight
Benjamin F
BF
Perry
John R B
JR
Elliott
Katherine S
KS
Hackett
Rachel
R
Guiducci
Candace
C
Shields
Beverley
B
Zeggini
Eleftheria
E
Lango
Hana
H
Lyssenko
Valeriya
V
Timpson
Nicholas J
NJ
Burtt
Noel P
NP
Rayner
Nigel W
NW
Saxena
Richa
R
Ardlie
Kristin
K
Tobias
Jonathan H
JH
Ness
Andrew R
AR
Ring
Susan M
SM
Palmer
Colin N A
CN
Morris
Andrew D
AD
Peltonen
Leena
L
Salomaa
Veikko
V
Davey Smith
George
G
Groop
Leif C
LC
Hattersley
Andrew T
AT
McCarthy
Mark I
MI
Hirschhorn
Joel N
JN
Frayling
Timothy M
TM
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
D025743:HMGA2 Protein