Genome-wide association analysis identifies 20 loci that influence adult height.
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.
Weedon
Michael N
MN
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK.
Lango
Hana
H
Lindgren
Cecilia M
CM
Wallace
Chris
C
Evans
David M
DM
Mangino
Massimo
M
Freathy
Rachel M
RM
Perry
John R B
JR
Stevens
Suzanne
S
Hall
Alistair S
AS
Samani
Nilesh J
NJ
Shields
Beverly
B
Prokopenko
Inga
I
Farrall
Martin
M
Dominiczak
Anna
A
Johnson
Toby
T
Bergmann
Sven
S
Beckmann
Jacques S
JS
Vollenweider
Peter
P
Waterworth
Dawn M
DM
Mooser
Vincent
V
Palmer
Colin N A
CN
Morris
Andrew D
AD
Ouwehand
Willem H
WH
Zhao
Jing Hua
JH
Li
Shengxu
S
Loos
Ruth J F
RJ
Barroso
Inês
I
Deloukas
Panagiotis
P
Sandhu
Manjinder S
MS
Wheeler
Eleanor
E
Soranzo
Nicole
N
Inouye
Michael
M
Wareham
Nicholas J
NJ
Caulfield
Mark
M
Munroe
Patricia B
PB
Hattersley
Andrew T
AT
McCarthy
Mark I
MI
Frayling
Timothy M
TM
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
D016326:Extracellular Matrix Proteins; D053823:Hedgehog Proteins; D009363:Neoplasm Proteins