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 Casey; Stephen 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

doi:10.1371/journal.pgen.1002298

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

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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 language	English (US)
Article number	e1002298
Journal	PLoS genetics
Volume	7
Issue number	10
DOIs	https://doi.org/10.1371/journal.pgen.1002298
State	Published - Oct 2011

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10.1371/journal.pgen.1002298

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N'Diaye, A., Chen, G. K., Palmer, C. D., Ge, B., Tayo, B., Mathias, R. A., Ding, J., Nalls, M. A., Adeyemo, A., Adoue, V., Ambrosone, C. B., Atwood, L., Bandera, E. V., Becker, L. C., Berndt, S. I., Bernstein, L., Blot, W. J., Boerwinkle, E., Britton, 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), Article e1002298. https://doi.org/10.1371/journal.pgen.1002298

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

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

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.",

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

year = "2011",

month = oct,

doi = "10.1371/journal.pgen.1002298",

language = "English (US)",

volume = "7",

journal = "PLoS genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "10",

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TY - JOUR

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.

PY - 2011/10

Y1 - 2011/10

N2 - 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.

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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DO - 10.1371/journal.pgen.1002298

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JO - PLoS genetics

JF - PLoS genetics

IS - 10

M1 - e1002298

ER -

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

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