학술논문
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.
Document Type
article
Author
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; 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; Kari E North
Source
PLoS Genetics, Vol 13, Iss 4, p e1006719 (2017)
Subject
Language
English
ISSN
1553-7390
1553-7404
1553-7404
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 < 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 (