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

Maggie C Y Ng, Mariaelisa Graff, Yingchang Lu, Anne E Justice, Poorva Mudgal, Ching-Ti Liu, Kristin Young, Lisa R Yanek, Mary F Feitosa, Mary K Wojczynski, Kristin Rand, Jennifer A Brody, Brian E Cade, Latchezar Dimitrov, Qing Duan, Xiuqing Guo, Leslie A Lange, Michael A Nalls, Hayrettin Okut, Salman M Tajuddin, Bamidele O Tayo, Sailaja Vedantam, Jonathan P Bradfield, Guanjie Chen, Wei-Min Chen, Alessandra Chesi, Marguerite R Irvin, Badri Padhukasahasram, Jennifer A Smith, Wei Zheng, Matthew A Allison, Christine B Ambrosone, Elisa V Bandera, Traci M Bartz, Sonja I Berndt, Leslie Bernstein, William J Blot, Erwin P Bottinger, John Carpten, Stephen J Chanock, Yii- Der Ida Chen, David V Conti, Richard S Cooper, Myriam Fornage, Barry I Freedman, Melissa Garcia, Phyllis J Goodman, Yu-Han H Hsu, Jennifer Hu, Chad D Huff, Sue A Ingles, Esther M John, Rick Kittles, Eric Klein, Jin Li, Barbara McKnight, Uma Nayak, Barbara Nemesure, Adesola Ogunniyi, Andrew Olshan, Michael F Press, Rebecca Rohde, Benjamin A Rybicki, Babatunde Salako, Maureen Sanderson, Yaming Shao, David S Siscovick, Janet L Stanford, Victoria L Stevens, Alex Stram, Sara S Strom, Dhananjay Vaidya, John S Witte, Jie Yao, Xiaofeng Zhu, Regina G Ziegler, Alan B Zonderman, Adebowale Adeyemo, Stefan Ambs, Mary Cushman, Jessica D Faul, Hakon Hakonarson, Albert M Levin, Katherine L Nathanson, Erin B Ware, David R Weir, Wei Zhao, Degui Zhi, The Bone Mineral Density in Childhood Study (BMDCS) Group, Donna K Arnett, Struan F A Grant, Sharon L R Kardia, Olufunmilayo I Oloapde, D C Rao, Charles N Rotimi, Michele M Sale, L Keoki Williams, Babette S Zemel, Diane M Becker, Ingrid B Borecki, Michele K Evans, Tamara B Harris, Joel N Hirschhorn, Yun Li, Sanjay R Patel, Bruce M Psaty, Jerome I Rotter, James G Wilson, Donald W Bowden, L Adrienne Cupples, Christopher A Haiman, Ruth J F Loos and Kari E North

PLOS Genetics, 2017, vol. 13, issue 4, 1-25

Abstract: 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 300 genetic regions that influence body size and shape as measured by body mass index (BMI) and waist-to-hip ratio (WHR), respectively, but few have been identified in populations of African ancestry. We conducted large scale high coverage GWAS and replication of these traits in 52,895 and 23,095 individuals of African ancestry, respectively, followed by additional replication in European populations. We identified 10 genome-wide significant loci in all individuals, and an additional seven loci by analyzing men and women separately. We combined African and European ancestry GWAS and were able to narrow down 43 out of 74 African ancestry associated genetic regions to contain small number of putative causal variants. Our results highlight the improvement of applying high density genome coverage and combining multiple ancestries in the identification and refinement of location of genetic regions associated with adiposity traits.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pgen00:1006719

DOI: 10.1371/journal.pgen.1006719

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