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

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Ng, Maggie C. Y.; Graff, Mariaelisa; Lu, Yingchang; Justice, Anne E.; Mudgal, Poorva; Liu, Ching-Ti; Young, Kristin L.; Yanek, Lisa R.; Feitosa, Mary F.; & Wojczynski, Mary K., et al. (2017). 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. PLOS Genetics, 13(4), e1006719. PMCID: PMC5419579

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 < 5x10-8: 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

URL

http://dx.doi.org/10.1371/journal.pgen.1006719

Reference Type

Journal Article

Year Published

2017

Journal Title

PLOS Genetics

Author(s)

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

PMCID

PMC5419579

ORCiD

Olshan - 0000-0001-9115-5128
Graff - 0000-0001-6380-1735