Genome-wide association analysis identifies 20 loci that influence adult height
Open accessAbstract
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.
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In height, the GIANT consortium confirmed inferences from 30,000 individuals when it expanded to 180,000, finding an additional 180 or so loci.
“in the case of height, the GIANT consortium (http://www.broadinstitute.org/collaboration/giant/) confirmed the inferences from 30,000 individuals100 when they jumped to 180,000, finding an additional 180 or so loci14.”
From Rare and common variants: twenty arguments (2012) · cites this paper as [100]
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- Authors
- Initiative, D. G., Weedon, M. N., The Wellcome Trust Case Control Consortium, Cambridge GEM Consortium, Lango, H., Lindgren, C. M., Wallace, C., Evans, D. M., Mangino, M., Freathy, R. M., Perry, J. R. B., Stevens, S., Hall, A. S., Samani, N. J., Shields, B., Prokopenko, I., Farrall, M., Dominiczak, A., Johnson, T., Bergmann, S., Beckmann, J. S., Vollenweider, P., Waterworth, D. M., Mooser, V., Palmer, C. N. A., Morris, A. D., Ouwehand, W. H., Caulfield, M., Munroe, P. B., Hattersley, A. T., McCarthy, M. I., & Frayling, T. M.
- Affiliations
- University of Exeter (GB)
- Centre for Human Genetics (GB)
- Queen Mary University of London (GB)
- University of Leicester (GB)
- University of Leeds (GB)
- British Heart Foundation (GB)
- SIB Swiss Institute of Bioinformatics (CH)
- Centre Hospitalier Universitaire Vaudois (CH)
- GlaxoSmithKline (United States) (US)
- University of Dundee (GB)
- National Health Service (GB)
- Corresponding author
- Frayling, Timothy M
- ORCID
- Weedon, Michael N
- Lindgren, Cecilia M
- Wallace, Chris
- Evans, David M
- Mangino, Massimo
- Freathy, Rachel M
- Perry, John R B
- Hall, Alistair S
- Samani, Nilesh J
- Prokopenko, Inga
- Farrall, Martin
- Dominiczak, Anna
- Johnson, Toby
- Beckmann, Jacques S
- Waterworth, Dawn M
- Mooser, Vincent
- Ouwehand, Willem H
- Caulfield, Mark
- Munroe, Patricia B
- Hattersley, Andrew T
- McCarthy, Mark I
- Frayling, Timothy M
- Venue
- Nature Genetics
- Published
- 2008-04-06
- Volume
- 40
- Issue
- 5
- Pages
- 575-583
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2681221
- OpenAlex
- W1998957301
- Cited by
- 826
- References
- 28
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 26 · 2023: 14 · 2022: 29 · 2021: 31 · 2020: 33 · 2019: 20 · 2018: 19 · 2017: 29 · 2016: 23 · 2015: 47 · 2014: 44 · 2013: 63 · 2012: 54
- FWCI
- 70.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IRIS (submittedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- Wellcome Trust (077011, 077016, 090532, 076113)
- British Heart Foundation (PG/02/128/14470, PG/02/128, FS/05/061/19501)
- Diabetes UK
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (116323, 112552, 3100AO-116323/1, 3100AO)
- Medical Research Council (G9521010D)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- adult height, polygenic traits, genetic loci, single nucleotide polymorphisms, human growth, Hedgehog signaling, extracellular matrix, CDK6, HMGA2, genetic architecture, quantitative trait genetics
- MeSH terms
- Adult, Aged, Body Height, Female, Genotype, Humans, Male, Middle Aged, Neoplasm Proteins, Genome, Human, Extracellular Matrix Proteins, Polymorphism, Single Nucleotide, Hedgehog Proteins
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