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