Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Mariaelisa Graff; Anne E. Justice; Kristin L. Young; Eirini Marouli; Xinruo Zhang; Rebecca S. Fine; Elise Lim; Victoria Buchanan; Kristin Rand; Mary F. Feitosa; Mary K. Wojczynski; Lisa R. Yanek; Yaming Shao; Rebecca Rohde; Adebowale A. Adeyemo; Melinda C. Aldrich; Matthew A. Allison; Christine B. Ambrosone; Stefan Ambs; Christopher Amos; Donna K. Arnett; Larry Atwood; Elisa V. Bandera; Traci Bartz; Diane M. Becker; Sonja I. Berndt; Leslie Bernstein; Lawrence F. Bielak; William J. Blot; Erwin P. Bottinger; Donald W. Bowden; Jonathan P. Bradfield; Jennifer A. Brody; Ulrich Broeckel; Gregory Burke; Brian E. Cade; Qiuyin Cai; Neil Caporaso; Chris Carlson; John Carpten; Graham Casey; Stephen J. Chanock; Guanjie Chen; Minhui Chen; Yii Der I. Chen; Wei Min Chen; Alessandra Chesi; Charleston W.K. Chiang; Lisa Chu; Gerry A. Coetzee; David V. Conti; Richard S. Cooper; Mary Cushman; Ellen Demerath; Sandra L. Deming; Latchezar Dimitrov; Jingzhong Ding; W. Ryan Diver; Qing Duan; Michele K. Evans; Adeyinka G. Falusi; Jessica D. Faul; Myriam Fornage; Caroline Fox; Barry I. Freedman; Melissa Garcia; Elizabeth M. Gillanders; Phyllis Goodman; Omri Gottesman; Struan F.A. Grant; Xiuqing Guo; Hakon Hakonarson; Talin Haritunians; Tamara B. Harris; Curtis C. Harris; Brian E. Henderson; Anselm Hennis; Dena G. Hernandez; Joel N. Hirschhorn; Lorna Haughton McNeill; Timothy D. Howard; Barbara Howard; Ann W. Hsing; Yu Han H. Hsu; Jennifer J. Hu; Chad D. Huff; Dezheng Huo; Sue A. Ingles; Marguerite R. Irvin; Esther M. John; Karen C. Johnson; Joanne M. Jordan; Edmond K. Kabagambe; Sun J. Kang; Sharon L. Kardia; Brendan J. Keating; Rick A. Kittles; Eric A. Klein; Suzanne Kolb; Laurence N. Kolonel; Charles Kooperberg; Lewis Kuller; Abdullah Kutlar; Leslie Lange; Carl D. Langefeld; Loic Le Marchand; Hampton Leonard; Guillaume Lettre; Albert M. Levin; Yun Li; Jin Li; Yongmei Liu; Youfang Liu; Simin Liu; Kurt Lohman; Vaneet Lotay; Yingchang Lu; William Maixner; Jo Ann E. Manson; Barbara McKnight; Yan Meng; Keri L. Monda; Kris Monroe; Jason H. Moore; Thomas H. Mosley; Poorva Mudgal; Adam B. Murphy; Rajiv Nadukuru; Mike A. Nalls; Katherine L. Nathanson; Uma Nayak; Amidou N'Diaye; Barbara Nemesure; Christine Neslund-Dudas; Marian L. Neuhouser; Sarah Nyante; Heather Ochs-Balcom; Temidayo O. Ogundiran; Adesola Ogunniyi; Oladosu Ojengbede; Hayrettin Okut; Olufunmilayo I. Olopade; Andrew Olshan; Badri Padhukasahasram; Julie Palmer; Cameron D. Palmer; Nicholette D. Palmer; George Papanicolaou; Sanjay R. Patel; Curtis A. Pettaway; Patricia A. Peyser; Michael F. Press; D. C. Rao; Laura J. Rasmussen-Torvik; Susan Redline; Alex P. Reiner; Suhn K. Rhie; Jorge L. Rodriguez-Gil; Charles N. Rotimi; Jerome I. Rotter; Edward A. Ruiz-Narvaez; Benjamin A. Rybicki; Babatunde Salako; Michele M. Sale; Maureen Sanderson; Eric Schadt; Pamela J. Schreiner; Claudia Schurmann; Ann G. Schwartz; Daniel A. Shriner; Lisa B. Signorello; Andrew B. Singleton; David S. Siscovick; Jennifer A. Smith; Shad Smith; Elizabeth Speliotes; Margaret Spitz; Janet L. Stanford; Victoria L. Stevens; Alex Stram; Sara S. Strom; Lara Sucheston; Yan V. Sun; Salman M. Tajuddin; Herman Taylor; Kira Taylor; Bamidele O. Tayo; Michael J. Thun; Margaret A. Tucker; Dhananjay Vaidya; David J. Van Den Berg; Sailaja Vedantam; Mara Vitolins; Zhaoming Wang; Erin B. Ware; Sylvia Wassertheil-Smoller; David R. Weir; John K. Wiencke; Scott M. Williams; L. Keoki Williams; James G. Wilson; John S. Witte; Margaret Wrensch; Xifeng Wu; Jie Yao; Neil Zakai; Krista Zanetti; Babette S. Zemel; Wei Zhao; Jing Hua Zhao; Wei Zheng; Degui Zhi; Jie Zhou; Xiaofeng Zhu; Regina G. Ziegler; Joe Zmuda; Alan B. Zonderman; Bruce M. Psaty; Ingrid B. Borecki; L. Adrienne Cupples; Ching Ti Liu; Christopher A. Haiman; Ruth Loos; Maggie C.Y. Ng; Kari E. North

doi:10.1016/j.ajhg.2021.02.011

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Mariaelisa Graff, Anne E. Justice, Kristin L. Young, Eirini Marouli, Xinruo Zhang, Rebecca S. Fine, Elise Lim, Victoria Buchanan, Kristin Rand, Mary F. Feitosa, Mary K. Wojczynski, Lisa R. Yanek, Yaming Shao, Rebecca Rohde, Adebowale A. Adeyemo, Melinda C. Aldrich, Matthew A. Allison, Christine B. Ambrosone, Stefan Ambs, Christopher AmosDonna K. Arnett, Larry Atwood, Elisa V. Bandera, Traci Bartz, Diane M. Becker, Sonja I. Berndt, Leslie Bernstein, Lawrence F. Bielak, William J. Blot, Erwin P. Bottinger, Donald W. Bowden, Jonathan P. Bradfield, Jennifer A. Brody, Ulrich Broeckel, Gregory Burke, Brian E. Cade, Qiuyin Cai, Neil Caporaso, Chris Carlson, John Carpten, Graham Casey, Stephen J. Chanock, Guanjie Chen, Minhui Chen, Yii Der I. Chen, Wei Min Chen, Alessandra Chesi, Charleston W.K. Chiang, Lisa Chu, Gerry A. Coetzee, David V. Conti, Richard S. Cooper, Mary Cushman, Ellen Demerath, Sandra L. Deming, Latchezar Dimitrov, Jingzhong Ding, W. Ryan Diver, Qing Duan, Michele K. Evans, Adeyinka G. Falusi, Jessica D. Faul, Myriam Fornage, Caroline Fox, Barry I. Freedman, Melissa Garcia, Elizabeth M. Gillanders, Phyllis Goodman, Omri Gottesman, Struan F.A. Grant, Xiuqing Guo, Hakon Hakonarson, Talin Haritunians, Tamara B. Harris, Curtis C. Harris, Brian E. Henderson, Anselm Hennis, Dena G. Hernandez, Joel N. Hirschhorn, Lorna Haughton McNeill, Timothy D. Howard, Barbara Howard, Ann W. Hsing, Yu Han H. Hsu, Jennifer J. Hu, Chad D. Huff, Dezheng Huo, Sue A. Ingles, Marguerite R. Irvin, Esther M. John, Karen C. Johnson, Joanne M. Jordan, Edmond K. Kabagambe, Sun J. Kang, Sharon L. Kardia, Brendan J. Keating, Rick A. Kittles, Eric A. Klein, Suzanne Kolb, Laurence N. Kolonel, Charles Kooperberg, Lewis Kuller, Abdullah Kutlar, Leslie Lange, Carl D. Langefeld, Loic Le Marchand, Hampton Leonard, Guillaume Lettre, Albert M. Levin, Yun Li, Jin Li, Yongmei Liu, Youfang Liu, Simin Liu, Kurt Lohman, Vaneet Lotay, Yingchang Lu, William Maixner, Jo Ann E. Manson, Barbara McKnight, Yan Meng, Keri L. Monda, Kris Monroe, Jason H. Moore, Thomas H. Mosley, Poorva Mudgal, Adam B. Murphy, Rajiv Nadukuru, Mike A. Nalls, Katherine L. Nathanson, Uma Nayak, Amidou N'Diaye, Barbara Nemesure, Christine Neslund-Dudas, Marian L. Neuhouser, Sarah Nyante, Heather Ochs-Balcom, Temidayo O. Ogundiran, Adesola Ogunniyi, Oladosu Ojengbede, Hayrettin Okut, Olufunmilayo I. Olopade, Andrew Olshan, Badri Padhukasahasram, Julie Palmer, Cameron D. Palmer, Nicholette D. Palmer, George Papanicolaou, Sanjay R. Patel, Curtis A. Pettaway, Patricia A. Peyser, Michael F. Press, D. C. Rao, Laura J. Rasmussen-Torvik, Susan Redline, Alex P. Reiner, Suhn K. Rhie, Jorge L. Rodriguez-Gil, Charles N. Rotimi, Jerome I. Rotter, Edward A. Ruiz-Narvaez, Benjamin A. Rybicki, Babatunde Salako, Michele M. Sale, Maureen Sanderson, Eric Schadt, Pamela J. Schreiner, Claudia Schurmann, Ann G. Schwartz, Daniel A. Shriner, Lisa B. Signorello, Andrew B. Singleton, David S. Siscovick, Jennifer A. Smith, Shad Smith, Elizabeth Speliotes, Margaret Spitz, Janet L. Stanford, Victoria L. Stevens, Alex Stram, Sara S. Strom, Lara Sucheston, Yan V. Sun, Salman M. Tajuddin, Herman Taylor, Kira Taylor, Bamidele O. Tayo, Michael J. Thun, Margaret A. Tucker, Dhananjay Vaidya, David J. Van Den Berg, Sailaja Vedantam, Mara Vitolins, Zhaoming Wang, Erin B. Ware, Sylvia Wassertheil-Smoller, David R. Weir, John K. Wiencke, Scott M. Williams, L. Keoki Williams, James G. Wilson, John S. Witte, Margaret Wrensch, Xifeng Wu, Jie Yao, Neil Zakai, Krista Zanetti, Babette S. Zemel, Wei Zhao, Jing Hua Zhao, Wei Zheng, Degui Zhi, Jie Zhou, Xiaofeng Zhu, Regina G. Ziegler, Joe Zmuda, Alan B. Zonderman, Bruce M. Psaty, Ingrid B. Borecki, L. Adrienne Cupples, Ching Ti Liu, Christopher A. Haiman, Ruth Loos, Maggie C.Y. Ng, Kari E. North

Pulmonary Disease

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

Original language	English (US)
Pages (from-to)	564-582
Number of pages	19
Journal	American journal of human genetics
Volume	108
Issue number	4
DOIs	https://doi.org/10.1016/j.ajhg.2021.02.011
State	Published - Apr 1 2021

Keywords

African ancestry
fine-mapping
genome-wide
height

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Access to Document

10.1016/j.ajhg.2021.02.011

Cite this

Graff, M., Justice, A. E., Young, K. L., Marouli, E., Zhang, X., Fine, R. S., Lim, E., Buchanan, V., Rand, K., Feitosa, M. F., Wojczynski, M. K., Yanek, L. R., Shao, Y., Rohde, R., Adeyemo, A. A., Aldrich, M. C., Allison, M. A., Ambrosone, C. B., Ambs, S., ... North, K. E. (2021). Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry. American journal of human genetics, 108(4), 564-582. https://doi.org/10.1016/j.ajhg.2021.02.011

Graff, M, Justice, AE, Young, KL, Marouli, E, Zhang, X, Fine, RS, Lim, E, Buchanan, V, Rand, K, Feitosa, MF, Wojczynski, MK, Yanek, LR, Shao, Y, Rohde, R, Adeyemo, AA, Aldrich, MC, Allison, MA, Ambrosone, CB, Ambs, S, Amos, C, Arnett, DK, Atwood, L, Bandera, EV, Bartz, T, Becker, DM, Berndt, SI, Bernstein, L, Bielak, LF, Blot, WJ, Bottinger, EP, Bowden, DW, Bradfield, JP, Brody, JA, Broeckel, U, Burke, G, Cade, BE, Cai, Q, Caporaso, N, Carlson, C, Carpten, J, Casey, G, Chanock, SJ, Chen, G, Chen, M, Chen, YDI, Chen, WM, Chesi, A, Chiang, CWK, Chu, L, Coetzee, GA, Conti, DV, Cooper, RS, Cushman, M, Demerath, E, Deming, SL, Dimitrov, L, Ding, J, Diver, WR, Duan, Q, Evans, MK, Falusi, AG, Faul, JD, Fornage, M, Fox, C, Freedman, BI, Garcia, M, Gillanders, EM, Goodman, P, Gottesman, O, Grant, SFA, Guo, X, Hakonarson, H, Haritunians, T, Harris, TB, Harris, CC, Henderson, BE, Hennis, A, Hernandez, DG, Hirschhorn, JN, McNeill, LH, Howard, TD, Howard, B, Hsing, AW, Hsu, YHH, Hu, JJ, Huff, CD, Huo, D, Ingles, SA, Irvin, MR, John, EM, Johnson, KC, Jordan, JM, Kabagambe, EK, Kang, SJ, Kardia, SL, Keating, BJ, Kittles, RA, Klein, EA, Kolb, S, Kolonel, LN, Kooperberg, C, Kuller, L, Kutlar, A, Lange, L, Langefeld, CD, Le Marchand, L, Leonard, H, Lettre, G, Levin, AM, Li, Y, Li, J, Liu, Y, Liu, Y, Liu, S, Lohman, K, Lotay, V, Lu, Y, Maixner, W, Manson, JAE, McKnight, B, Meng, Y, Monda, KL, Monroe, K, Moore, JH, Mosley, TH, Mudgal, P, Murphy, AB, Nadukuru, R, Nalls, MA, Nathanson, KL, Nayak, U, N'Diaye, A, Nemesure, B, Neslund-Dudas, C, Neuhouser, ML, Nyante, S, Ochs-Balcom, H, Ogundiran, TO, Ogunniyi, A, Ojengbede, O, Okut, H, Olopade, OI, Olshan, A, Padhukasahasram, B, Palmer, J, Palmer, CD, Palmer, ND, Papanicolaou, G, Patel, SR, Pettaway, CA, Peyser, PA, Press, MF, Rao, DC, Rasmussen-Torvik, LJ, Redline, S, Reiner, AP, Rhie, SK, Rodriguez-Gil, JL, Rotimi, CN, Rotter, JI, Ruiz-Narvaez, EA, Rybicki, BA, Salako, B, Sale, MM, Sanderson, M, Schadt, E, Schreiner, PJ, Schurmann, C, Schwartz, AG, Shriner, DA, Signorello, LB, Singleton, AB, Siscovick, DS, Smith, JA, Smith, S, Speliotes, E, Spitz, M, Stanford, JL, Stevens, VL, Stram, A, Strom, SS, Sucheston, L, Sun, YV, Tajuddin, SM, Taylor, H, Taylor, K, Tayo, BO, Thun, MJ, Tucker, MA, Vaidya, D, Van Den Berg, DJ, Vedantam, S, Vitolins, M, Wang, Z, Ware, EB, Wassertheil-Smoller, S, Weir, DR, Wiencke, JK, Williams, SM, Williams, LK, Wilson, JG, Witte, JS, Wrensch, M, Wu, X, Yao, J, Zakai, N, Zanetti, K, Zemel, BS, Zhao, W, Zhao, JH, Zheng, W, Zhi, D, Zhou, J, Zhu, X, Ziegler, RG, Zmuda, J, Zonderman, AB, Psaty, BM, Borecki, IB, Cupples, LA, Liu, CT, Haiman, CA, Loos, R, Ng, MCY & North, KE 2021, 'Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry', American journal of human genetics, vol. 108, no. 4, pp. 564-582. https://doi.org/10.1016/j.ajhg.2021.02.011

@article{8b6cee7ea6e84aca8e4bc6553a38148f,

title = "Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry",

abstract = "Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.",

keywords = "African ancestry, fine-mapping, genome-wide, height",

author = "Mariaelisa Graff and Justice, {Anne E.} and Young, {Kristin L.} and Eirini Marouli and Xinruo Zhang and Fine, {Rebecca S.} and Elise Lim and Victoria Buchanan and Kristin Rand and Feitosa, {Mary F.} and Wojczynski, {Mary K.} and Yanek, {Lisa R.} and Yaming Shao and Rebecca Rohde and Adeyemo, {Adebowale A.} and Aldrich, {Melinda C.} and Allison, {Matthew A.} and Ambrosone, {Christine B.} and Stefan Ambs and Christopher Amos and Arnett, {Donna K.} and Larry Atwood and Bandera, {Elisa V.} and Traci Bartz and Becker, {Diane M.} and Berndt, {Sonja I.} and Leslie Bernstein and Bielak, {Lawrence F.} and Blot, {William J.} and Bottinger, {Erwin P.} and Bowden, {Donald W.} and Bradfield, {Jonathan P.} and Brody, {Jennifer A.} and Ulrich Broeckel and Gregory Burke and Cade, {Brian E.} and Qiuyin Cai and Neil Caporaso and Chris Carlson and John Carpten and Graham Casey and Chanock, {Stephen J.} and Guanjie Chen and Minhui Chen and Chen, {Yii Der I.} and Chen, {Wei Min} and Alessandra Chesi and Chiang, {Charleston W.K.} and Lisa Chu and Coetzee, {Gerry A.} and Conti, {David V.} and Cooper, {Richard S.} and Mary Cushman and Ellen Demerath and Deming, {Sandra L.} and Latchezar Dimitrov and Jingzhong Ding and Diver, {W. Ryan} and Qing Duan and Evans, {Michele K.} and Falusi, {Adeyinka G.} and Faul, {Jessica D.} and Myriam Fornage and Caroline Fox and Freedman, {Barry I.} and Melissa Garcia and Gillanders, {Elizabeth M.} and Phyllis Goodman and Omri Gottesman and Grant, {Struan F.A.} and Xiuqing Guo and Hakon Hakonarson and Talin Haritunians and Harris, {Tamara B.} and Harris, {Curtis C.} and Henderson, {Brian E.} and Anselm Hennis and Hernandez, {Dena G.} and Hirschhorn, {Joel N.} and McNeill, {Lorna Haughton} and Howard, {Timothy D.} and Barbara Howard and Hsing, {Ann W.} and Hsu, {Yu Han H.} and Hu, {Jennifer J.} and Huff, {Chad D.} and Dezheng Huo and Ingles, {Sue A.} and Irvin, {Marguerite R.} and John, {Esther M.} and Johnson, {Karen C.} and Jordan, {Joanne M.} and Kabagambe, {Edmond K.} and Kang, {Sun J.} and Kardia, {Sharon L.} and Keating, {Brendan J.} and Kittles, {Rick A.} and Klein, {Eric A.} and Suzanne Kolb and Kolonel, {Laurence N.} and Charles Kooperberg and Lewis Kuller and Abdullah Kutlar and Leslie Lange and Langefeld, {Carl D.} and {Le Marchand}, Loic and Hampton Leonard and Guillaume Lettre and Levin, {Albert M.} and Yun Li and Jin Li and Yongmei Liu and Youfang Liu and Simin Liu and Kurt Lohman and Vaneet Lotay and Yingchang Lu and William Maixner and Manson, {Jo Ann E.} and Barbara McKnight and Yan Meng and Monda, {Keri L.} and Kris Monroe and Moore, {Jason H.} and Mosley, {Thomas H.} and Poorva Mudgal and Murphy, {Adam B.} and Rajiv Nadukuru and Nalls, {Mike A.} and Nathanson, {Katherine L.} and Uma Nayak and Amidou N'Diaye and Barbara Nemesure and Christine Neslund-Dudas and Neuhouser, {Marian L.} and Sarah Nyante and Heather Ochs-Balcom and Ogundiran, {Temidayo O.} and Adesola Ogunniyi and Oladosu Ojengbede and Hayrettin Okut and Olopade, {Olufunmilayo I.} and Andrew Olshan and Badri Padhukasahasram and Julie Palmer and Palmer, {Cameron D.} and Palmer, {Nicholette D.} and George Papanicolaou and Patel, {Sanjay R.} and Pettaway, {Curtis A.} and Peyser, {Patricia A.} and Press, {Michael F.} and Rao, {D. C.} and Rasmussen-Torvik, {Laura J.} and Susan Redline and Reiner, {Alex P.} and Rhie, {Suhn K.} and Rodriguez-Gil, {Jorge L.} and Rotimi, {Charles N.} and Rotter, {Jerome I.} and Ruiz-Narvaez, {Edward A.} and Rybicki, {Benjamin A.} and Babatunde Salako and Sale, {Michele M.} and Maureen Sanderson and Eric Schadt and Schreiner, {Pamela J.} and Claudia Schurmann and Schwartz, {Ann G.} and Shriner, {Daniel A.} and Signorello, {Lisa B.} and Singleton, {Andrew B.} and Siscovick, {David S.} and Smith, {Jennifer A.} and Shad Smith and Elizabeth Speliotes and Margaret Spitz and Stanford, {Janet L.} and Stevens, {Victoria L.} and Alex Stram and Strom, {Sara S.} and Lara Sucheston and Sun, {Yan V.} and Tajuddin, {Salman M.} and Herman Taylor and Kira Taylor and Tayo, {Bamidele O.} and Thun, {Michael J.} and Tucker, {Margaret A.} and Dhananjay Vaidya and {Van Den Berg}, {David J.} and Sailaja Vedantam and Mara Vitolins and Zhaoming Wang and Ware, {Erin B.} and Sylvia Wassertheil-Smoller and Weir, {David R.} and Wiencke, {John K.} and Williams, {Scott M.} and Williams, {L. Keoki} and Wilson, {James G.} and Witte, {John S.} and Margaret Wrensch and Xifeng Wu and Jie Yao and Neil Zakai and Krista Zanetti and Zemel, {Babette S.} and Wei Zhao and Zhao, {Jing Hua} and Wei Zheng and Degui Zhi and Jie Zhou and Xiaofeng Zhu and Ziegler, {Regina G.} and Joe Zmuda and Zonderman, {Alan B.} and Psaty, {Bruce M.} and Borecki, {Ingrid B.} and Cupples, {L. Adrienne} and Liu, {Ching Ti} and Haiman, {Christopher A.} and Ruth Loos and Ng, {Maggie C.Y.} and North, {Kari E.}",

note = "Publisher Copyright: {\textcopyright} 2021 American Society of Human Genetics",

year = "2021",

month = apr,

day = "1",

doi = "10.1016/j.ajhg.2021.02.011",

language = "English (US)",

volume = "108",

pages = "564--582",

journal = "American journal of human genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

AU - Graff, Mariaelisa

AU - Justice, Anne E.

AU - Young, Kristin L.

AU - Marouli, Eirini

AU - Zhang, Xinruo

AU - Fine, Rebecca S.

AU - Lim, Elise

AU - Buchanan, Victoria

AU - Rand, Kristin

AU - Feitosa, Mary F.

AU - Wojczynski, Mary K.

AU - Yanek, Lisa R.

AU - Shao, Yaming

AU - Rohde, Rebecca

AU - Adeyemo, Adebowale A.

AU - Aldrich, Melinda C.

AU - Allison, Matthew A.

AU - Ambrosone, Christine B.

AU - Ambs, Stefan

AU - Amos, Christopher

AU - Arnett, Donna K.

AU - Atwood, Larry

AU - Bandera, Elisa V.

AU - Bartz, Traci

AU - Becker, Diane M.

AU - Berndt, Sonja I.

AU - Bernstein, Leslie

AU - Bielak, Lawrence F.

AU - Blot, William J.

AU - Bottinger, Erwin P.

AU - Bowden, Donald W.

AU - Bradfield, Jonathan P.

AU - Brody, Jennifer A.

AU - Broeckel, Ulrich

AU - Burke, Gregory

AU - Cade, Brian E.

AU - Cai, Qiuyin

AU - Caporaso, Neil

AU - Carlson, Chris

AU - Carpten, John

AU - Casey, Graham

AU - Chanock, Stephen J.

AU - Chen, Guanjie

AU - Chen, Minhui

AU - Chen, Yii Der I.

AU - Chen, Wei Min

AU - Chesi, Alessandra

AU - Chiang, Charleston W.K.

AU - Chu, Lisa

AU - Coetzee, Gerry A.

AU - Conti, David V.

AU - Cooper, Richard S.

AU - Cushman, Mary

AU - Demerath, Ellen

AU - Deming, Sandra L.

AU - Dimitrov, Latchezar

AU - Ding, Jingzhong

AU - Diver, W. Ryan

AU - Duan, Qing

AU - Evans, Michele K.

AU - Falusi, Adeyinka G.

AU - Faul, Jessica D.

AU - Fornage, Myriam

AU - Fox, Caroline

AU - Freedman, Barry I.

AU - Garcia, Melissa

AU - Gillanders, Elizabeth M.

AU - Goodman, Phyllis

AU - Gottesman, Omri

AU - Grant, Struan F.A.

AU - Guo, Xiuqing

AU - Hakonarson, Hakon

AU - Haritunians, Talin

AU - Harris, Tamara B.

AU - Harris, Curtis C.

AU - Henderson, Brian E.

AU - Hennis, Anselm

AU - Hernandez, Dena G.

AU - Hirschhorn, Joel N.

AU - McNeill, Lorna Haughton

AU - Howard, Timothy D.

AU - Howard, Barbara

AU - Hsing, Ann W.

AU - Hsu, Yu Han H.

AU - Hu, Jennifer J.

AU - Huff, Chad D.

AU - Huo, Dezheng

AU - Ingles, Sue A.

AU - Irvin, Marguerite R.

AU - John, Esther M.

AU - Johnson, Karen C.

AU - Jordan, Joanne M.

AU - Kabagambe, Edmond K.

AU - Kang, Sun J.

AU - Kardia, Sharon L.

AU - Keating, Brendan J.

AU - Kittles, Rick A.

AU - Klein, Eric A.

AU - Kolb, Suzanne

AU - Kolonel, Laurence N.

AU - Kooperberg, Charles

AU - Kuller, Lewis

AU - Kutlar, Abdullah

AU - Lange, Leslie

AU - Langefeld, Carl D.

AU - Le Marchand, Loic

AU - Leonard, Hampton

AU - Lettre, Guillaume

AU - Levin, Albert M.

AU - Li, Yun

AU - Li, Jin

AU - Liu, Yongmei

AU - Liu, Youfang

AU - Liu, Simin

AU - Lohman, Kurt

AU - Lotay, Vaneet

AU - Lu, Yingchang

AU - Maixner, William

AU - Manson, Jo Ann E.

AU - McKnight, Barbara

AU - Meng, Yan

AU - Monda, Keri L.

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AU - Singleton, Andrew B.

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AU - Smith, Jennifer A.

AU - Smith, Shad

AU - Speliotes, Elizabeth

AU - Spitz, Margaret

AU - Stanford, Janet L.

AU - Stevens, Victoria L.

AU - Stram, Alex

AU - Strom, Sara S.

AU - Sucheston, Lara

AU - Sun, Yan V.

AU - Tajuddin, Salman M.

AU - Taylor, Herman

AU - Taylor, Kira

AU - Tayo, Bamidele O.

AU - Thun, Michael J.

AU - Tucker, Margaret A.

AU - Vaidya, Dhananjay

AU - Van Den Berg, David J.

AU - Vedantam, Sailaja

AU - Vitolins, Mara

AU - Wang, Zhaoming

AU - Ware, Erin B.

AU - Wassertheil-Smoller, Sylvia

AU - Weir, David R.

AU - Wiencke, John K.

AU - Williams, Scott M.

AU - Williams, L. Keoki

AU - Wilson, James G.

AU - Witte, John S.

AU - Wrensch, Margaret

AU - Wu, Xifeng

AU - Yao, Jie

AU - Zakai, Neil

AU - Zanetti, Krista

AU - Zemel, Babette S.

AU - Zhao, Wei

AU - Zhao, Jing Hua

AU - Zheng, Wei

AU - Zhi, Degui

AU - Zhou, Jie

AU - Zhu, Xiaofeng

AU - Ziegler, Regina G.

AU - Zmuda, Joe

AU - Zonderman, Alan B.

AU - Psaty, Bruce M.

AU - Borecki, Ingrid B.

AU - Cupples, L. Adrienne

AU - Liu, Ching Ti

AU - Haiman, Christopher A.

AU - Loos, Ruth

AU - Ng, Maggie C.Y.

AU - North, Kari E.

PY - 2021/4/1

Y1 - 2021/4/1

N2 - Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

AB - Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

KW - African ancestry

KW - fine-mapping

KW - genome-wide

KW - height

UR - http://www.scopus.com/inward/record.url?scp=85103409847&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85103409847&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2021.02.011

DO - 10.1016/j.ajhg.2021.02.011

M3 - Article

C2 - 33713608

AN - SCOPUS:85103409847

SN - 0002-9297

VL - 108

SP - 564

EP - 582

JO - American journal of human genetics

JF - American journal of human genetics

IS - 4

ER -

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

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