%0 Journal Article %J The American Journal of Human Genetics %D 2021 %T Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry. %A Graff, Mariaelisa %A Justice, Anne E %A Young, Kristin L %A Marouli, Eirini %A Zhang, Xinruo %A Fine, Rebecca S %A Lim, Elise %A Buchanan, Victoria %A Rand, Kristin %A Feitosa, Mary F %A Wojczynski, Mary K %A Yanek, Lisa R %A Shao, Yaming %A Rohde, Rebecca %A Adeyemo, Adebowale A %A Aldrich, Melinda C %A Matthew A. Allison %A Ambrosone, Christine B %A Ambs, Stefan %A Amos, Christopher %A Donna K Arnett %A Atwood, Larry %A Bandera, Elisa V %A Traci M Bartz %A Becker, Diane M %A Berndt, Sonja I %A Bernstein, Leslie %A Bielak, Lawrence F %A Blot, William J %A Erwin P Bottinger %A Bowden, Donald W %A Bradfield, Jonathan P %A Brody, Jennifer A %A Broeckel, Ulrich %A Burke, Gregory %A Brian E Cade %A Cai, Qiuyin %A Caporaso, Neil %A Carlson, Chris %A John Carpten %A Casey, Graham %A Chanock, Stephen J %A Chen, Guanjie %A Chen, Minhui %A Chen, Yii-Der I %A Chen, Wei-Min %A Chesi, Alessandra %A Chiang, Charleston W K %A Chu, Lisa %A Coetzee, Gerry A %A Conti, David V %A Cooper, Richard S %A Cushman, Mary %A Ellen W Demerath %A Deming, Sandra L %A Dimitrov, Latchezar %A Ding, Jingzhong %A Diver, W Ryan %A Duan, Qing %A Michele K Evans %A Falusi, Adeyinka G %A Jessica Faul %A Myriam Fornage %A Caroline S Fox %A Freedman, Barry I %A Garcia, Melissa %A Gillanders, Elizabeth M %A Phyllis J Goodman %A Gottesman, Omri %A Grant, Struan F A %A Guo, Xiuqing %A Hakonarson, Hakon %A Haritunians, Talin %A Tamara B Harris %A Harris, Curtis C %A Henderson, Brian E %A Hennis, Anselm %A Dena G Hernandez %A Hirschhorn, Joel N %A McNeill, Lorna Haughton %A Howard, Timothy D %A Howard, Barbara %A Hsing, Ann W %A Hsu, Yu-Han H %A Hu, Jennifer J %A Huff, Chad D %A Huo, Dezheng %A Ingles, Sue A %A Irvin, Marguerite R %A John, Esther M %A Johnson, Karen C %A Jordan, Joanne M %A Kabagambe, Edmond K %A Kang, Sun J %A Sharon L R Kardia %A Keating, Brendan J %A Rick A Kittles %A Eric A Klein %A Kolb, Suzanne %A Kolonel, Laurence N %A Charles Kooperberg %A Kuller, Lewis %A Kutlar, Abdullah %A Leslie A Lange %A Langefeld, Carl D %A Loic Le Marchand %A Leonard, Hampton %A Lettre, Guillaume %A Levin, Albert M %A Li, Yun %A Li, Jin %A Liu, Yongmei %A Liu, Youfang %A Liu, Simin %A Kurt Lohman %A Lotay, Vaneet %A Lu, Yingchang %A Maixner, William %A JoAnn E Manson %A McKnight, Barbara %A Meng, Yan %A Monda, Keri L %A Monroe, Kris %A Moore, Jason H %A Thomas H Mosley %A Mudgal, Poorva %A Murphy, Adam B %A Nadukuru, Rajiv %A Michael A Nalls %A Nathanson, Katherine L %A Nayak, Uma %A N'Diaye, Amidou %A Nemesure, Barbara %A Neslund-Dudas, Christine %A Neuhouser, Marian L %A Nyante, Sarah %A Ochs-Balcom, Heather %A Ogundiran, Temidayo O %A Ogunniyi, Adesola %A Ojengbede, Oladosu %A Okut, Hayrettin %A Olopade, Olufunmilayo I %A Olshan, Andrew %A Padhukasahasram, Badri %A Palmer, Julie %A Palmer, Cameron D %A Palmer, Nicholette D %A George J Papanicolaou %A Patel, Sanjay R %A Pettaway, Curtis A %A Peyser, Patricia A %A Press, Michael F %A Rao, D C %A Rasmussen-Torvik, Laura J %A Redline, Susan %A Reiner, Alex P %A Rhie, Suhn K %A Rodriguez-Gil, Jorge L %A Charles N Rotimi %A Rotter, Jerome I %A Ruiz-Narvaez, Edward A %A Rybicki, Benjamin A %A Babatunde Salako %A Sale, Michele M %A Sanderson, Maureen %A Eric E Schadt %A Schreiner, Pamela J %A Schurmann, Claudia %A Schwartz, Ann G %A Daniel Shriner %A Signorello, Lisa B %A Andrew B Singleton %A David S Siscovick %A Smith, Jennifer A %A Smith, Shad %A Elizabeth K Speliotes %A Spitz, Margaret %A Stanford, Janet L %A Stevens, Victoria L %A Stram, Alex %A Strom, Sara S %A Sucheston, Lara %A Yan V Sun %A Tajuddin, Salman M %A Taylor, Herman %A Taylor, Kira %A Bamidele O Tayo %A Michael J Thun %A Tucker, Margaret A %A Vaidya, Dhananjay %A Van Den Berg, David J %A Vedantam, Sailaja %A Vitolins, Mara %A Wang, Zhaoming %A Erin B Ware %A Wassertheil-Smoller, Sylvia %A David R Weir %A Wiencke, John K %A Williams, Scott M %A L Keoki Williams %A Wilson, James G %A Witte, John S %A Wrensch, Margaret %A Wu, Xifeng %A Yao, Jie %A Zakai, Neil %A Zanetti, Krista %A Zemel, Babette S %A Zhao, Wei %A Jing Hua Zhao %A Zheng, Wei %A Zhi, Degui %A Zhou, Jie %A Zhu, Xiaofeng %A Ziegler, Regina G %A Zmuda, Joe %A Alan B Zonderman %A Psaty, Bruce M %A Ingrid B Borecki %A Cupples, L Adrienne %A Liu, Ching-Ti %A Christopher A Haiman %A Ruth J F Loos %A Ng, Maggie C Y %A Kari E North %K Africa %K African Americans %K Blacks %K Body Height %K Europe %K Female %K Genome-Wide Association Study %K Humans %K Male %K Polymorphism, Single Nucleotide %X

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.

%B The American Journal of Human Genetics %V 108 %P 564-582 %G eng %N 4 %R 10.1016/j.ajhg.2021.02.011 %0 Journal Article %J PLoS Genetics %D 2017 %T Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium. %A Ng, Maggie C Y %A Graff, Mariaelisa %A Lu, Yingchang %A Justice, Anne E %A Mudgal, Poorva %A Liu, Ching-Ti %A Young, Kristin %A Yanek, Lisa R %A Feitosa, Mary F %A Wojczynski, Mary K %A Rand, Kristin %A Brody, Jennifer A %A Brian E Cade %A Dimitrov, Latchezar %A Duan, Qing %A Guo, Xiuqing %A Leslie A Lange %A Michael A Nalls %A Okut, Hayrettin %A Tajuddin, Salman M %A Bamidele O Tayo %A Vedantam, Sailaja %A Bradfield, Jonathan P %A Chen, Guanjie %A Chen, Wei-Min %A Chesi, Alessandra %A Irvin, Marguerite R %A Padhukasahasram, Badri %A Smith, Jennifer A %A Zheng, Wei %A Matthew A. Allison %A Ambrosone, Christine B %A Bandera, Elisa V %A Traci M Bartz %A Berndt, Sonja I %A Bernstein, Leslie %A Blot, William J %A Erwin P Bottinger %A John Carpten %A Chanock, Stephen J %A Chen, Yii-Der Ida %A Conti, David V %A Cooper, Richard S %A Myriam Fornage %A Freedman, Barry I %A Garcia, Melissa %A Phyllis J Goodman %A Hsu, Yu-Han H %A Hu, Jennifer %A Huff, Chad D %A Ingles, Sue A %A John, Esther M %A Rick A Kittles %A Eric A Klein %A Li, Jin %A McKnight, Barbara %A Nayak, Uma %A Nemesure, Barbara %A Ogunniyi, Adesola %A Olshan, Andrew %A Press, Michael F %A Rohde, Rebecca %A Rybicki, Benjamin A %A Babatunde Salako %A Sanderson, Maureen %A Shao, Yaming %A David S Siscovick %A Stanford, Janet L %A Stevens, Victoria L %A Stram, Alex %A Strom, Sara S %A Vaidya, Dhananjay %A Witte, John S %A Yao, Jie %A Zhu, Xiaofeng %A Ziegler, Regina G %A Alan B Zonderman %A Adeyemo, Adebowale %A Ambs, Stefan %A Cushman, Mary %A Jessica Faul %A Hakonarson, Hakon %A Levin, Albert M %A Nathanson, Katherine L %A Erin B Ware %A David R Weir %A Zhao, Wei %A Zhi, Degui %A Donna K Arnett %A Grant, Struan F A %A Sharon L R Kardia %A Oloapde, Olufunmilayo I %A Rao, D C %A Charles N Rotimi %A Sale, Michele M %A L Keoki Williams %A Zemel, Babette S %A Becker, Diane M %A Ingrid B Borecki %A Michele K Evans %A Tamara B Harris %A Hirschhorn, Joel N %A Li, Yun %A Patel, Sanjay R %A Psaty, Bruce M %A Rotter, Jerome I %A Wilson, James G %A Bowden, Donald W %A Cupples, L Adrienne %A Christopher A Haiman %A Ruth J F Loos %A Kari E North %K Adiposity %K Anthropometry %K Blacks %K Body Mass Index %K Chromosome Mapping %K Female %K Gene Frequency %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Humans %K Linkage Disequilibrium %K Male %K Obesity %K Polymorphism, Single Nucleotide %K Serine Endopeptidases %K Transcription Factor 7-Like 2 Protein %K Waist-Hip Ratio %K Whites %X

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.

%B PLoS Genetics %V 13 %P e1006719 %G eng %N 4 %R 10.1371/journal.pgen.1006719