Genome-wide association analysis identifies 20 loci that influence adult height

Michael N. Weedon; Hana Lango; Cecilia M. Lindgren; Chris Wallace; David M. Evans; Massimo Mangino; Rachel M. Freathy; John R. B. Perry; Suzanne Stevens; Alistair S. Hall; Nilesh J. Samani; Beverly Shields; Inga Prokopenko; Martin Farrall; Anna Dominiczak; Toby Johnson; Sven Bergmann; Jacques S. Beckmann; Peter Vollenweider; Dawn M. Waterworth; Vincent Mooser; Colin N. A. Palmer; Andrew D. Morris; Willem H. Ouwehand; Mark Caulfield; Patricia B. Munroe; Andrew T. Hattersley; Mark I. McCarthy; Timothy M. Frayling; Wellcome Trust Case Control Consor, Cambridge GEM Consortium, Diabet Genetics Initiat

doi:10.1038/ng.121

Genome-wide association analysis identifies 20 loci that influence adult height

Michael N. Weedon, Hana Lango, Cecilia M. Lindgren, Chris Wallace, David M. Evans, Massimo Mangino, Rachel M. Freathy, John R. B. Perry, Suzanne Stevens, Alistair S. Hall, Nilesh J. Samani, Beverly Shields, Inga Prokopenko, Martin Farrall, Anna Dominiczak, Toby Johnson, Sven Bergmann, Jacques S. Beckmann, Peter Vollenweider, Dawn M. WaterworthVincent Mooser, Colin N. A. Palmer, Andrew D. Morris, Willem H. Ouwehand, Mark Caulfield, Patricia B. Munroe, Andrew T. Hattersley, Mark I. McCarthy, Timothy M. Frayling, Wellcome Trust Case Control Consor, Cambridge GEM Consortium, Diabet Genetics Initiat

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647 Citations (Scopus)

Abstract

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 iota x 10(-10)). Combined, the 20 SNPs explain similar to 3% of height variation, with a similar to 5 cm difference between the 6.2% of people with iota 7 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.

Original language	English
Pages (from-to)	575-583
Number of pages	9
Journal	Nature Genetics
Volume	40
Issue number	5
DOIs	https://doi.org/10.1038/ng.121
Publication status	Published - May 2008

Keywords

GENETIC ASSOCIATION
BODY HEIGHT
SUSCEPTIBILITY
POPULATION
STRATIFICATION
OSTEOARTHRITIS
HERITABILITY
EXPRESSION
STATURE
COHORTS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Weedon, M. N., 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., ... Wellcome Trust Case Control Consor, Cambridge GEM Consortium, Diabet Genetics Initiat (2008). Genome-wide association analysis identifies 20 loci that influence adult height. Nature Genetics, 40(5), 575-583. https://doi.org/10.1038/ng.121

@article{99b1f226a3194b57a1f389afe4428b68,

title = "Genome-wide association analysis identifies 20 loci that influence adult height",

abstract = "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 iota x 10(-10)). Combined, the 20 SNPs explain similar to 3% of height variation, with a similar to 5 cm difference between the 6.2% of people with iota 7 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.",

keywords = "GENETIC ASSOCIATION, BODY HEIGHT, SUSCEPTIBILITY, POPULATION, STRATIFICATION, OSTEOARTHRITIS, HERITABILITY, EXPRESSION, STATURE, COHORTS",

author = "Weedon, {Michael N.} and Hana Lango and Lindgren, {Cecilia M.} and Chris Wallace and Evans, {David M.} and Massimo Mangino and Freathy, {Rachel M.} and Perry, {John R. B.} and Suzanne Stevens and Hall, {Alistair S.} and Samani, {Nilesh J.} and Beverly Shields and Inga Prokopenko and Martin Farrall and Anna Dominiczak and Toby Johnson and Sven Bergmann and Beckmann, {Jacques S.} and Peter Vollenweider and Waterworth, {Dawn M.} and Vincent Mooser and Palmer, {Colin N. A.} and Morris, {Andrew D.} and Ouwehand, {Willem H.} and Mark Caulfield and Munroe, {Patricia B.} and Hattersley, {Andrew T.} and McCarthy, {Mark I.} and Frayling, {Timothy M.} and {Wellcome Trust Case Control Consor, Cambridge GEM Consortium, Diabet Genetics Initiat}",

year = "2008",

month = may,

doi = "10.1038/ng.121",

language = "English",

volume = "40",

pages = "575--583",

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issn = "1061-4036",

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Weedon, MN, Lango, H, Lindgren, CM, Wallace, C, Evans, DM, Mangino, M, Freathy, RM, Perry, JRB, Stevens, S, Hall, AS, Samani, NJ, Shields, B, Prokopenko, I, Farrall, M, Dominiczak, A, Johnson, T, Bergmann, S, Beckmann, JS, Vollenweider, P, Waterworth, DM, Mooser, V, Palmer, CNA, Morris, AD, Ouwehand, WH, Caulfield, M, Munroe, PB, Hattersley, AT, McCarthy, MI, Frayling, TM & Wellcome Trust Case Control Consor, Cambridge GEM Consortium, Diabet Genetics Initiat 2008, 'Genome-wide association analysis identifies 20 loci that influence adult height', Nature Genetics, vol. 40, no. 5, pp. 575-583. https://doi.org/10.1038/ng.121

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T1 - Genome-wide association analysis identifies 20 loci that influence adult height

AU - Weedon, Michael N.

AU - Lango, Hana

AU - Lindgren, Cecilia M.

AU - Wallace, Chris

AU - Evans, David M.

AU - Mangino, Massimo

AU - Freathy, Rachel M.

AU - Perry, John R. B.

AU - Stevens, Suzanne

AU - Hall, Alistair S.

AU - Samani, Nilesh J.

AU - Shields, Beverly

AU - Prokopenko, Inga

AU - Farrall, Martin

AU - Dominiczak, Anna

AU - Johnson, Toby

AU - Bergmann, Sven

AU - Beckmann, Jacques S.

AU - Vollenweider, Peter

AU - Waterworth, Dawn M.

AU - Mooser, Vincent

AU - Palmer, Colin N. A.

AU - Morris, Andrew D.

AU - Ouwehand, Willem H.

AU - Caulfield, Mark

AU - Munroe, Patricia B.

AU - Hattersley, Andrew T.

AU - McCarthy, Mark I.

AU - Frayling, Timothy M.

AU - Wellcome Trust Case Control Consor, Cambridge GEM Consortium, Diabet Genetics Initiat

PY - 2008/5

Y1 - 2008/5

N2 - 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 iota x 10(-10)). Combined, the 20 SNPs explain similar to 3% of height variation, with a similar to 5 cm difference between the 6.2% of people with iota 7 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.

AB - 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 iota x 10(-10)). Combined, the 20 SNPs explain similar to 3% of height variation, with a similar to 5 cm difference between the 6.2% of people with iota 7 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.

KW - GENETIC ASSOCIATION

KW - BODY HEIGHT

KW - SUSCEPTIBILITY

KW - POPULATION

KW - STRATIFICATION

KW - OSTEOARTHRITIS

KW - HERITABILITY

KW - EXPRESSION

KW - STATURE

KW - COHORTS

U2 - 10.1038/ng.121

DO - 10.1038/ng.121

M3 - Article

C2 - 18391952

SN - 1061-4036

VL - 40

SP - 575

EP - 583

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Genome-wide association analysis identifies 20 loci that influence adult height

Abstract

Keywords

UN SDGs

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