Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry
2021; Elsevier BV; Volume: 108; Issue: 4 Linguagem: Inglês
10.1016/j.ajhg.2021.02.011
ISSN1537-6605
AutoresMariaelisa Graff, Anne E. Justice, Kristin L. Young, Eirini Marouli, Xinruo Zhang, Rebecca S. Fine, Elise Lim, Victoria L. Buchanan, Kristin A. Rand, Mary F. Feitosa, Mary K. Wojczynski, Lisa R. Yanek, Yaming Shao, Rebecca Rohde, Adebowale Adeyemo, Melinda C. Aldrich, Matthew Allison, Christine B. Ambrosone, Stefan Ambs, Christopher I. Amos, Donna K. Arnett, Larry D. Atwood, Elisa V. Bandera, Traci M. Bartz, Diane M. Becker, Sonja I. Berndt, Leslie Bernstein, Lawrence F. Bielak, William J. Blot, Erwin P. Böttinger, Donald W. Bowden, Jonathan P. Bradfield, Jennifer A. Brody, Ulrich Broeckel, Gregory L. Burke, Brian E. Cade, Qiuyin Cai, Neil E. Caporaso, Chris Carlson, John D. Carpten, Graham Casey, Stephen J. Chanock, Guanjie Chen, Minhui Chen, Yii-Der I. Chen, Wei‐Min Chen, Alessandra Chesi, Charleston W. K. Chiang, Lisa W. Chu, Gerhard A. Coetzee, David V. Conti, Stephen S. Rich, Mary Cushman, Ellen W. 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 S. Fox, Barry I. Freedman, Melissa García, Elizabeth M. Gillanders, Phyllis J. Goodman, Omri Gottesman, Struan F.A. Grant, Xiuqing Guo, Hákon Hákonarson, Talin Haritunians, Tamara B. Harris, Curtis C. Harris, Brian E. Henderson, Anselm Hennis, Dena Hernández, Joel N. Hirschhorn, Lorna H. McNeill, Timothy D. Howard, Barbara V. Howard, Ann W. Hsing, Yu-Han H. Hsu, Jennifer J. Hu, Chad Huff, Dezheng Huo, Sue A. Ingles, Marguerite R. Irvin, Esther M. John, Karen Johnson, Joanne M. Jordan, Edmond K. Kabagambe, Sun Jung Kang, Sharon L.R. Kardia, Brendan J. Keating, Rick A. Kittles, Eric A. Klein, Suzanne Kolb, Laurence N. Kolonel, Charles Kooperberg, Lewis H. Kuller, Abdullah Kutlar, Leslie A. Lange, Carl D. Langefeld, Loı̈c Le Marchand, Hampton L. Leonard, Guillaume Lettre, Albert M. Levin, Yun Li, Jin Li, Yongmei Liu, Youfang Liu, Simin Liu, Kurt Lohman, Vaneet Lotay, Yingchang Lu, William Maixner, JoAnn 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 J. Nyante, Heather M. Ochs‐Balcom, Temidayo O. Ogundiran, Adesola Ogunniyi, Oladosu Ojengbede, Hayrettin Okut, Olufunmilayo I. Olopade, Andrew F. Olshan, Badri Padhukasahasram, Julie R. 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‐Narváez, Benjamin A. Rybicki, Babatunde Salako, Michèle M. Sale, Maureen Sanderson, Eric E. Schadt, Pamela J. Schreiner, Claudia Schurmann, Ann G. Schwartz, Daniel Shriner, Lisa B. Signorello, Andrew B. Singleton, David S. Siscovick, Jennifer A. Smith, Shad B. Smith, Elizabeth K. Speliotes, Margaret R. Spitz, Janet L. Stanford, Victoria L. Stevens, Alex Stram, Sara S. Strom, Lara Sucheston, Yan V. Sun, Salman M. Tajuddin, Herman A. Taylor, Kira C. Taylor, Bamidele O. Tayo, Michael J. Thun, Margaret A. Tucker, Dhananjay Vaidya, David J. Van Den Berg, Sailaja Vedantam, Mara Z. Vitolins, Thomas J. 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 A. Zakai, Krista A. Zanetti, Babette S. Zemel, Wei Zhao, Jing Hua Zhao, Wei Zheng, Degui Zhi, Jie Zhou, Xiaofeng Zhu, Regina G. Ziegler, J.M. Zmuda, Alan B. Zonderman, Bruce M. Psaty, Ingrid B. Borecki, L. Adrienne Cupples, Yongmei Liu, Christopher A. Haiman, Ruth J. F. Loos, Maggie Ng, Kari E. North,
Tópico(s)Genetic Mapping and Diversity in Plants and Animals
ResumoAlthough 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.
Referência(s)