Common variants in the GDF5-UQCC region are associated with variation in human height.
Identifying genetic variants that influence human height will advance our understanding of skeletal growth and development. Several rare genetic variants have been convincingly and reproducibly associated with height in mendelian syndromes, and common variants in the transcription factor gene HMGA2 are associated with variation in height in the general population. Here we report genome-wide association analyses, using genotyped and imputed markers, of 6,669 individuals from Finland and Sardinia, and follow-up analyses in an additional 28,801 individuals. We show that common variants in the osteoarthritis-associated locus GDF5-UQCC contribute to variation in height with an estimated additive effect of 0.44 cm (overall P < 10(-15)). Our results indicate that there may be a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development.
Sanna
Serena
S
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Jackson
Anne U
AU
Nagaraja
Ramaiah
R
Willer
Cristen J
CJ
Chen
Wei-Min
WM
Bonnycastle
Lori L
LL
Shen
Haiqing
H
Timpson
Nicholas
N
Lettre
Guillaume
G
Usala
Gianluca
G
Chines
Peter S
PS
Stringham
Heather M
HM
Scott
Laura J
LJ
Dei
Mariano
M
Lai
Sandra
S
Albai
Giuseppe
G
Crisponi
Laura
L
Naitza
Silvia
S
Doheny
Kimberly F
KF
Pugh
Elizabeth W
EW
Ben-Shlomo
Yoav
Y
Ebrahim
Shah
S
Lawlor
Debbie A
DA
Bergman
Richard N
RN
Watanabe
Richard M
RM
Uda
Manuela
M
Tuomilehto
Jaakko
J
Coresh
Josef
J
Hirschhorn
Joel N
JN
Shuldiner
Alan R
AR
Schlessinger
David
D
Collins
Francis S
FS
Davey Smith
George
G
Boerwinkle
Eric
E
Cao
Antonio
A
Boehnke
Michael
M
Abecasis
Gonçalo R
GR
Mohlke
Karen L
KL
D020121:5' Untranslated Regions; D001741:Black or African American; D000368:Aged; D000483:Alleles; D001827:Body Height / Q000235:genetics*; D015992:Body Mass Index; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D002890:Chromosomes, Human, Pair 20; D015986:Confounding Factors, Epidemiologic; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D015894:Genome, Human; D055428:Growth Differentiation Factor 5; D025743:HMGA2 Protein / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D011994:Recombinant Proteins / Q000378:metabolism; D012044:Regression Analysis
D020121:5' Untranslated Regions; D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; D005819:Genetic Markers; D055428:Growth Differentiation Factor 5; D025743:HMGA2 Protein; D011994:Recombinant Proteins