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PMID: 18193045 Published · ppublish English Comparative Study Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Common variants in the GDF5-UQCC region are associated with variation in human height.

Nature genetics ·Vol. 40 ·No. 2 ·2008-02-00 ·Pages 198-203

Sanna S, Jackson AU, Nagaraja R, Willer CJ, Chen WM, Bonnycastle LL, Shen H, Timpson N, Lettre G, Usala G, Chines PS, Stringham HM, Scott LJ, Dei M, Lai S, Albai G, Crisponi L, Naitza S, Doheny KF, Pugh EW, Ben-Shlomo Y, Ebrahim S, Lawlor DA, Bergman RN, Watanabe RM, Uda M, Tuomilehto J, Coresh J, Hirschhorn JN, Shuldiner AR, Schlessinger D, Collins FS, Davey Smith G, Boerwinkle E, Cao A, Boehnke M, Abecasis GR, Mohlke KL

Abstract

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.

MeSH Terms
5' Untranslated Regions African Americans Aged Alleles Body Height/genetics Body Mass Index Bone Morphogenetic Proteins/genetics,metabolism Chromosomes, Human, Pair 20 Confounding Factors, Epidemiologic Female Gene Dosage Gene Frequency Genetic Markers Genetic Variation Genome, Human Growth Differentiation Factor 5 HMGA2 Protein/genetics Haplotypes Humans Linkage Disequilibrium Male Middle Aged Osteoarthritis/genetics Polymorphism, Single Nucleotide Probability Recombinant Proteins/metabolism Regression Analysis
Chemicals
5' Untranslated Regions Bone Morphogenetic Proteins GDF5 protein, human Genetic Markers Growth Differentiation Factor 5 HMGA2 Protein Recombinant Proteins
Authors & Affiliations
38 authors, click to expand affiliations / ORCID
Sanna Serena
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Jackson Anne U
Nagaraja Ramaiah
Willer Cristen J
Chen Wei-Min
Bonnycastle Lori L
Shen Haiqing
Timpson Nicholas
Lettre Guillaume
Usala Gianluca
Chines Peter S
Stringham Heather M
Scott Laura J
Dei Mariano
Lai Sandra
Albai Giuseppe
Crisponi Laura
Naitza Silvia
Doheny Kimberly F
Pugh Elizabeth W
Ben-Shlomo Yoav
Ebrahim Shah
Lawlor Debbie A
Bergman Richard N
Watanabe Richard M
Uda Manuela
Tuomilehto Jaakko
Coresh Josef
Hirschhorn Joel N
Shuldiner Alan R
Schlessinger David
Collins Francis S
Davey Smith George
Boerwinkle Eric
Cao Antonio
Boehnke Michael
Abecasis Gonçalo R
Mohlke Karen L
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.74
Published
2008-02-00
Epub
2008-00-13
Pages
198-203
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2914680
Subset
IM
Grants
NHLBI NIH HHS · N01HC55020 · United States
NIAMS NIH HHS · R01 AR046838 · United States
Medical Research Council · G0000934 · United Kingdom
NHGRI NIH HHS · R01 HG002651 · United States
NHLBI NIH HHS · N01-HC-55016 · United States
NIDDK NIH HHS · R01 DK072193 · United States
NHLBI NIH HHS · HL72515 · United States
NHLBI NIH HHS · N01HC55015 · United States
NIDDK NIH HHS · R01 DK062370 · United States
NHLBI NIH HHS · N01-HC-55019 · United States
NHLBI NIH HHS · N01-HC-55015 · United States
Intramural NIH HHS · Z01 HG000024 · United States
NIDDK NIH HHS · U01 DK062370 · United States
NIDDK NIH HHS · R01 DK072193-04 · United States
NIAMS NIH HHS · AR046838 · United States
NHLBI NIH HHS · U01 HL084729-03 · United States
NIA NIH HHS · R01 AG018728 · United States
NIDDK NIH HHS · R56 DK062370 · United States
NHGRI NIH HHS · N01HG65403 · United States
NHLBI NIH HHS · N01HC55018 · United States
NHLBI NIH HHS · U01 HL084729 · United States
Medical Research Council · G0600705 · United Kingdom
NHLBI NIH HHS · N01-HC-55022 · United States
Wellcome Trust · 068545/Z/02 · United Kingdom
NHLBI NIH HHS · N01HC55022 · United States
NHGRI NIH HHS · HG002651 · United States
NCRR NIH HHS · M01 RR 16500 · United States
NHLBI NIH HHS · N01-HC-55021 · United States
NIDDK NIH HHS · DK072193 · United States
NHLBI NIH HHS · HL084729 · United States
NIDDK NIH HHS · P30 DK072488 · United States
NIDDK NIH HHS · R01 DK029867 · United States
NHLBI NIH HHS · N01-HC-55020 · United States
NIDDK NIH HHS · DK54361 · United States
NHLBI NIH HHS · N01HC55016 · United States
NHLBI NIH HHS · U01 HL072515 · United States
NHGRI NIH HHS · R01 HG002651-05S2 · United States
NCRR NIH HHS · M01 RR016500 · United States
NIA NIH HHS · AG18728 · United States
NIDDK NIH HHS · DK062370 · United States
NHLBI NIH HHS · N01HC55019 · United States
NHLBI NIH HHS · N01-HC-55018 · United States
NHLBI NIH HHS · N01HC55021 · United States
Databases
RefSeq
NM_000557, NM_018244
External Links
PubMed source DOI: 10.1038/ng.74 PMC Full Text View journal details
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