학술논문
Trans-ethnic fine-mapping of genetic loci for body mass index in the diverse ancestral populations of the Population Architecture using Genomics and Epidemiology (PAGE) Study reveals evidence for multiple signals at established loci
Document Type
article
Author
Fernández-Rhodes, Lindsay; Gong, Jian; Haessler, Jeffrey; Franceschini, Nora; Graff, Mariaelisa; Nishimura, Katherine K; Wang, Yujie; Highland, Heather M; Yoneyama, Sachiko; Bush, William S; Goodloe, Robert; Ritchie, Marylyn D; Crawford, Dana; Gross, Myron; Fornage, Myriam; Buzkova, Petra; Tao, Ran; Isasi, Carmen; Avilés-Santa, Larissa; Daviglus, Martha; Mackey, Rachel H; Houston, Denise; Gu, C Charles; Ehret, Georg; Nguyen, Khanh-Dung H; Lewis, Cora E; Leppert, Mark; Irvin, Marguerite R; Lim, Unhee; Haiman, Christopher A; Le Marchand, Loic; Schumacher, Fredrick; Wilkens, Lynne; Lu, Yingchang; Bottinger, Erwin P; Loos, Ruth JL; Sheu, Wayne H-H; Guo, Xiuqing; Lee, Wen-Jane; Hai, Yang; Hung, Yi-Jen; Absher, Devin; Wu, I-Chien; Taylor, Kent D; Lee, I-Te; Liu, Yeheng; Wang, Tzung-Dau; Quertermous, Thomas; Juang, Jyh-Ming J; Rotter, Jerome I; Assimes, Themistocles; Hsiung, Chao A; Chen, Yii-Der Ida; Prentice, Ross; Kuller, Lewis H; Manson, JoAnn E; Kooperberg, Charles; Smokowski, Paul; Robinson, Whitney R; Gordon-Larsen, Penny; Li, Rongling; Hindorff, Lucia; Buyske, Steven; Matise, Tara C; Peters, Ulrike; North, Kari E
Source
Human Genetics. 136(6)
Subject
Language
Abstract
Most body mass index (BMI) genetic loci have been identified in studies of primarily European ancestries. The effect of these loci in other racial/ethnic groups is less clear. Thus, we aimed to characterize the generalizability of 170 established BMI variants, or their proxies, to diverse US populations and trans-ethnically fine-map 36 BMI loci using a sample of >102,000 adults of African, Hispanic/Latino, Asian, European and American Indian/Alaskan Native descent from the Population Architecture using Genomics and Epidemiology Study. We performed linear regression of the natural log of BMI (18.5-70 kg/m2) on the additive single nucleotide polymorphisms (SNPs) at BMI loci on the MetaboChip (Illumina, Inc.), adjusting for age, sex, population stratification, study site, or relatedness. We then performed fixed-effect meta-analyses and a Bayesian trans-ethnic meta-analysis to empirically cluster by allele frequency differences. Finally, we approximated conditional and joint associations to test for the presence of secondary signals. We noted directional consistency with the previously reported risk alleles beyond what would have been expected by chance (binomial p