Identification, replication, and fine-mapping of loci associated with adult height in individuals of African ancestry

Amidou N'Diaye, Gary K. Chen, Cameron D. Palmer, Bing Ge, Bamidele Tayo, Rasika A. Mathias, Jingzhong Ding, Michael A. Nalls, Adebowale Adeyemo, Véronique Adoue, Christine B. Ambrosone, Larry Atwood, Elisa V. Bandera, Lewis C. Becker, Sonja I. Berndt, Leslie Bernstein, William J. Blot, Eric Boerwinkle, Angela Britton, Graham CaseyStephen J. Chanock, Ellen Demerath, Sandra L. Deming, W. Ryan Diver, Caroline Fox, Tamara B. Harris, Dena G. Hernandez, Jennifer J. Hu, Sue A. Ingles, Esther M. John, Craig Johnson, Brendan Keating, Rick A Kittles, Laurence N. Kolonel, Stephen B. Kritchevsky, Loic Marchand, Kurt Lohman, Jiankang Liu, Robert C. Millikan, Adam Murphy, Solomon Musani, Christine Neslund-Dudas, Kari E. North, Sarah Nyante, Adesola Ogunniyi, Elaine A. Ostrander, George Papanicolaou, Sanjay Patel, Curtis A. Pettaway, Michael F. Press, Susan Redline, Jorge L. Rodriguez-Gil, Charles Rotimi, Benjamin A. Rybicki, Babatunde Salako, Pamela J. Schreiner, Lisa B. Signorello, Andrew B. Singleton, Janet L. Stanford, Alex H. Stram, Daniel O. Stram, Sara S. Strom, Bhoom Suktitipat, Michael J. Thun, John S. Witte, Lisa R. Yanek, Regina G. Ziegler, Wei Zheng, Xiaofeng Zhu, Joseph M. Zmuda, Alan B. Zonderman, Michele K. Evans, Yongmei Liu, Diane M. Becker, Richard S. Cooper, Tomi Pastinen, Brian E. Henderson, Joel N. Hirschhorn, Guillaume Lettre, Christopher A. Haiman

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Adult height is a classic polygenic trait of high heritability (h 2 ~0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ~10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10 -12 and 2p14-rs4315565, P = 1.2×10 -8). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10 -4 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits.

Original languageEnglish (US)
Article numbere1002298
JournalPLoS Genetics
Volume7
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

Fingerprint

ancestry
Single Nucleotide Polymorphism
loci
Multifactorial Inheritance
Population
African Americans
single nucleotide polymorphism
Meta-Analysis
polymorphism
Genome
Gene Expression
African American
etiology
meta-analysis
heritability
human diseases
genome
gene expression
gene

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

N'Diaye, A., Chen, G. K., Palmer, C. D., Ge, B., Tayo, B., Mathias, R. A., ... Haiman, C. A. (2011). Identification, replication, and fine-mapping of loci associated with adult height in individuals of African ancestry. PLoS Genetics, 7(10), [e1002298]. https://doi.org/10.1371/journal.pgen.1002298

Identification, replication, and fine-mapping of loci associated with adult height in individuals of African ancestry. / N'Diaye, Amidou; Chen, Gary K.; Palmer, Cameron D.; Ge, Bing; Tayo, Bamidele; Mathias, Rasika A.; Ding, Jingzhong; Nalls, Michael A.; Adeyemo, Adebowale; Adoue, Véronique; Ambrosone, Christine B.; Atwood, Larry; Bandera, Elisa V.; Becker, Lewis C.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Boerwinkle, Eric; Britton, Angela; Casey, Graham; Chanock, Stephen J.; Demerath, Ellen; Deming, Sandra L.; Diver, W. Ryan; Fox, Caroline; Harris, Tamara B.; Hernandez, Dena G.; Hu, Jennifer J.; Ingles, Sue A.; John, Esther M.; Johnson, Craig; Keating, Brendan; Kittles, Rick A; Kolonel, Laurence N.; Kritchevsky, Stephen B.; Marchand, Loic; Lohman, Kurt; Liu, Jiankang; Millikan, Robert C.; Murphy, Adam; Musani, Solomon; Neslund-Dudas, Christine; North, Kari E.; Nyante, Sarah; Ogunniyi, Adesola; Ostrander, Elaine A.; Papanicolaou, George; Patel, Sanjay; Pettaway, Curtis A.; Press, Michael F.; Redline, Susan; Rodriguez-Gil, Jorge L.; Rotimi, Charles; Rybicki, Benjamin A.; Salako, Babatunde; Schreiner, Pamela J.; Signorello, Lisa B.; Singleton, Andrew B.; Stanford, Janet L.; Stram, Alex H.; Stram, Daniel O.; Strom, Sara S.; Suktitipat, Bhoom; Thun, Michael J.; Witte, John S.; Yanek, Lisa R.; Ziegler, Regina G.; Zheng, Wei; Zhu, Xiaofeng; Zmuda, Joseph M.; Zonderman, Alan B.; Evans, Michele K.; Liu, Yongmei; Becker, Diane M.; Cooper, Richard S.; Pastinen, Tomi; Henderson, Brian E.; Hirschhorn, Joel N.; Lettre, Guillaume; Haiman, Christopher A.

In: PLoS Genetics, Vol. 7, No. 10, e1002298, 10.2011.

Research output: Contribution to journalArticle

N'Diaye, A, Chen, GK, Palmer, CD, Ge, B, Tayo, B, Mathias, RA, Ding, J, Nalls, MA, Adeyemo, A, Adoue, V, Ambrosone, CB, Atwood, L, Bandera, EV, Becker, LC, Berndt, SI, Bernstein, L, Blot, WJ, Boerwinkle, E, Britton, A, Casey, G, Chanock, SJ, Demerath, E, Deming, SL, Diver, WR, Fox, C, Harris, TB, Hernandez, DG, Hu, JJ, Ingles, SA, John, EM, Johnson, C, Keating, B, Kittles, RA, Kolonel, LN, Kritchevsky, SB, Marchand, L, Lohman, K, Liu, J, Millikan, RC, Murphy, A, Musani, S, Neslund-Dudas, C, North, KE, Nyante, S, Ogunniyi, A, Ostrander, EA, Papanicolaou, G, Patel, S, Pettaway, CA, Press, MF, Redline, S, Rodriguez-Gil, JL, Rotimi, C, Rybicki, BA, Salako, B, Schreiner, PJ, Signorello, LB, Singleton, AB, Stanford, JL, Stram, AH, Stram, DO, Strom, SS, Suktitipat, B, Thun, MJ, Witte, JS, Yanek, LR, Ziegler, RG, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Evans, MK, Liu, Y, Becker, DM, Cooper, RS, Pastinen, T, Henderson, BE, Hirschhorn, JN, Lettre, G & Haiman, CA 2011, 'Identification, replication, and fine-mapping of loci associated with adult height in individuals of African ancestry', PLoS Genetics, vol. 7, no. 10, e1002298. https://doi.org/10.1371/journal.pgen.1002298
N'Diaye, Amidou ; Chen, Gary K. ; Palmer, Cameron D. ; Ge, Bing ; Tayo, Bamidele ; Mathias, Rasika A. ; Ding, Jingzhong ; Nalls, Michael A. ; Adeyemo, Adebowale ; Adoue, Véronique ; Ambrosone, Christine B. ; Atwood, Larry ; Bandera, Elisa V. ; Becker, Lewis C. ; Berndt, Sonja I. ; Bernstein, Leslie ; Blot, William J. ; Boerwinkle, Eric ; Britton, Angela ; Casey, Graham ; Chanock, Stephen J. ; Demerath, Ellen ; Deming, Sandra L. ; Diver, W. Ryan ; Fox, Caroline ; Harris, Tamara B. ; Hernandez, Dena G. ; Hu, Jennifer J. ; Ingles, Sue A. ; John, Esther M. ; Johnson, Craig ; Keating, Brendan ; Kittles, Rick A ; Kolonel, Laurence N. ; Kritchevsky, Stephen B. ; Marchand, Loic ; Lohman, Kurt ; Liu, Jiankang ; Millikan, Robert C. ; Murphy, Adam ; Musani, Solomon ; Neslund-Dudas, Christine ; North, Kari E. ; Nyante, Sarah ; Ogunniyi, Adesola ; Ostrander, Elaine A. ; Papanicolaou, George ; Patel, Sanjay ; Pettaway, Curtis A. ; Press, Michael F. ; Redline, Susan ; Rodriguez-Gil, Jorge L. ; Rotimi, Charles ; Rybicki, Benjamin A. ; Salako, Babatunde ; Schreiner, Pamela J. ; Signorello, Lisa B. ; Singleton, Andrew B. ; Stanford, Janet L. ; Stram, Alex H. ; Stram, Daniel O. ; Strom, Sara S. ; Suktitipat, Bhoom ; Thun, Michael J. ; Witte, John S. ; Yanek, Lisa R. ; Ziegler, Regina G. ; Zheng, Wei ; Zhu, Xiaofeng ; Zmuda, Joseph M. ; Zonderman, Alan B. ; Evans, Michele K. ; Liu, Yongmei ; Becker, Diane M. ; Cooper, Richard S. ; Pastinen, Tomi ; Henderson, Brian E. ; Hirschhorn, Joel N. ; Lettre, Guillaume ; Haiman, Christopher A. / Identification, replication, and fine-mapping of loci associated with adult height in individuals of African ancestry. In: PLoS Genetics. 2011 ; Vol. 7, No. 10.
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T1 - Identification, replication, and fine-mapping of loci associated with adult height in individuals of African ancestry

AU - N'Diaye, Amidou

AU - Chen, Gary K.

AU - Palmer, Cameron D.

AU - Ge, Bing

AU - Tayo, Bamidele

AU - Mathias, Rasika A.

AU - Ding, Jingzhong

AU - Nalls, Michael A.

AU - Adeyemo, Adebowale

AU - Adoue, Véronique

AU - Ambrosone, Christine B.

AU - Atwood, Larry

AU - Bandera, Elisa V.

AU - Becker, Lewis C.

AU - Berndt, Sonja I.

AU - Bernstein, Leslie

AU - Blot, William J.

AU - Boerwinkle, Eric

AU - Britton, Angela

AU - Casey, Graham

AU - Chanock, Stephen J.

AU - Demerath, Ellen

AU - Deming, Sandra L.

AU - Diver, W. Ryan

AU - Fox, Caroline

AU - Harris, Tamara B.

AU - Hernandez, Dena G.

AU - Hu, Jennifer J.

AU - Ingles, Sue A.

AU - John, Esther M.

AU - Johnson, Craig

AU - Keating, Brendan

AU - Kittles, Rick A

AU - Kolonel, Laurence N.

AU - Kritchevsky, Stephen B.

AU - Marchand, Loic

AU - Lohman, Kurt

AU - Liu, Jiankang

AU - Millikan, Robert C.

AU - Murphy, Adam

AU - Musani, Solomon

AU - Neslund-Dudas, Christine

AU - North, Kari E.

AU - Nyante, Sarah

AU - Ogunniyi, Adesola

AU - Ostrander, Elaine A.

AU - Papanicolaou, George

AU - Patel, Sanjay

AU - Pettaway, Curtis A.

AU - Press, Michael F.

AU - Redline, Susan

AU - Rodriguez-Gil, Jorge L.

AU - Rotimi, Charles

AU - Rybicki, Benjamin A.

AU - Salako, Babatunde

AU - Schreiner, Pamela J.

AU - Signorello, Lisa B.

AU - Singleton, Andrew B.

AU - Stanford, Janet L.

AU - Stram, Alex H.

AU - Stram, Daniel O.

AU - Strom, Sara S.

AU - Suktitipat, Bhoom

AU - Thun, Michael J.

AU - Witte, John S.

AU - Yanek, Lisa R.

AU - Ziegler, Regina G.

AU - Zheng, Wei

AU - Zhu, Xiaofeng

AU - Zmuda, Joseph M.

AU - Zonderman, Alan B.

AU - Evans, Michele K.

AU - Liu, Yongmei

AU - Becker, Diane M.

AU - Cooper, Richard S.

AU - Pastinen, Tomi

AU - Henderson, Brian E.

AU - Hirschhorn, Joel N.

AU - Lettre, Guillaume

AU - Haiman, Christopher A.

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AB - Adult height is a classic polygenic trait of high heritability (h 2 ~0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ~10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10 -12 and 2p14-rs4315565, P = 1.2×10 -8). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10 -4 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits.

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