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Discovery and fine-mapping of height loci using high density imputation of genome-wide association studies in individuals of African ancestry – the African Ancestry Anthropometry Genetics Consortium

Citation

Graff, Mariaelisa; Justice, Anne E.; Young, Kristin L.; Marouli, Eirini; Zhang, Xinrou; Fine, Rebecca S.; Lim, Elise; Buchanan, Victoria; Rand, Kristin A.; & Feitosa, Mary F., et al. (Forthcoming). Discovery and fine-mapping of height loci using high density imputation of genome-wide association studies in individuals of African ancestry – the African Ancestry Anthropometry Genetics Consortium. American Journal of Human Genetics.

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 sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and variants 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 and ECD/FAM149B1) in sex-combined results and two loci (CRB1 and KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, and 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. Only two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequency <5%. Of 801 known European height signals, 645 demonstrated directionally consistent associations with height, of which 205 were nominally statistically significant (P<0.05) in the African 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.

Reference Type

Journal Article

Article Type

Regular

Year Published

Forthcoming

Journal Title

American Journal of Human Genetics

Author(s)

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

Data Set/Study

African Ancestry Anthropometry Genetics Consortium (AAAGC)
European genome -wide association study (GWAS)