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

TitleDiscovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.
Publication TypeJournal Article
Year of Publication2021
AuthorsGraff, 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, Y-derI, Chen, W-M, Chesi, A, Chiang, CWK, Chu, L, Coetzee, GA, Conti, DV, Cooper, RS, Cushman, M, Demerath, E, Deming, SL, Dimitrov, L, Ding, J, W Diver, R, 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, LHaughton, Howard, TD, Howard, B, Hsing, AW, Hsu, Y-HH, 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, iv, 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, L Williams, K, 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, AL, Liu, C-T, Haiman, CA, Loos, R, C Y Ng, M, North, KE
JournalAm J Hum Genet
Volume108
Issue4
Pagination564-582
Date Published2021 Apr 01
ISSN1537-6605
Abstract<p>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.</p>
DOI10.1016/j.ajhg.2021.02.011
Alternate JournalAm J Hum Genet
PubMed ID33713608
Grant ListR01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL143885 / HL / NHLBI NIH HHS / United States
T32 GM008692 / GM / NIGMS NIH HHS / United States
ePub date: 
21/04