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Generalization and Fine Mapping of European Ancestry-Based Central Adiposity Variants in African Ancestry Populations

Citation

Yoneyama, Sachiko; Yao, Jie; Guo, Xiuqing; Fernandez-Rhodes, Lindsay; Lim, Unhee; Boston, Jonathan; Buzkova, Petra; Carlson, Christopher S.; Cheng, Iona; & Cochran, Barbara J., et al. (2017). Generalization and Fine Mapping of European Ancestry-Based Central Adiposity Variants in African Ancestry Populations. International Journal of Obesity, 41(2), 324-331. PMCID: PMC5296276

Abstract

BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of BMI and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition.
SUBJECTS/METHODS: To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine mapping cardiovascular associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants.
RESULTS: Of the 17 WHR loci, eight SNPs located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses.
CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.

URL

http://dx.doi.org/10.1038/ijo.2016.207

Reference Type

Journal Article

Year Published

2017

Journal Title

International Journal of Obesity

Author(s)

Yoneyama, Sachiko
Yao, Jie
Guo, Xiuqing
Fernandez-Rhodes, Lindsay
Lim, Unhee
Boston, Jonathan
Buzkova, Petra
Carlson, Christopher S.
Cheng, Iona
Cochran, Barbara J.
Cooper, Richard S.
Ehret, Georg B.
Fornage, Myriam
Gong, Jian
Gross, Myron D.
Gu, C. Charles
Haessler, Jeffrey
Haiman, Christopher A.
Henderson, Brian E.
Hindorff, Lucia A.
Houston, Denise K.
Irvin, Marguerite Ryan
Jackson, Rebecca D.
Kuller, Lewis H.
Leppert, Mark F.
Lewis, Cora E.
Li, Rongling L.
Le Marchand, Loic
Matise, Tara C.
Nguyen, Khanh-Dung H.
Chakravarti, Aravinda
Pankow, James S.
Pankratz, Nathan
Pooler, Loreall C.
Ritchie, Marylyn D.
Bien, Stephanie A.
Wassel, Christina L.
Chen, Yii-Der Ida
Taylor, Kent D.
Allison, Matthew A.
Rotter, Jerome I.
Schreiner, Pamela J.
Schumacher, Fredrick R.
Wilkens, Lynne R.
Boerwinkle, Eric A.
Kooperberg, Charles L.
Peters, Ulrike
Buyske, Steven G.
Graff, Mariaelisa
North, Kari E.

PMCID

PMC5296276