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Int J Obes (Lond). 2017 Feb;41(2):324-331. doi: 10.1038/ijo.2016.207. Epub 2016 Nov 21.

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.

Author information

1
Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
2
Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
3
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
4
Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA.
5
Department of Biostatistics, University of Washington, Seattle, WA, USA.
6
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
7
Cancer Prevention Institute of California, Fremont, CA, USA.
8
Baylor College of Medicine, Houston, TX, USA.
9
Division of Cardiology, Geneva University Hospital, Genève, Switzerland.
10
Department of Public Health Sciences, Loyola University, Chicago, IL, USA.
11
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
12
The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
13
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
14
Department of Biostatistics, Washington University, St Louis, MO, USA.
15
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
16
Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
17
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
18
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
19
Department of Internal Medicine, Ohio State Medical Center, Columbus, OH, USA.
20
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
21
Department of Human Genetics, University of Utah, Salt Lake City, UT, USA.
22
Department of Medicine, University of Alabama, Birmingham, AL, USA.
23
Department of Genetics, Rutgers University, Piscataway, NJ, USA.
24
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
25
Department of Biochemistry and Molecular Biology, Pennsylvania State University, State College, PA, USA.
26
Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Colchester, VT, USA.
27
Department of Preventive Medicine, School of Medicine, University of California San Diego, San Diego, CA, USA.
28
The Human Genetics Center and Institute of Molecular Medicine, Houston, TX, USA.
29
Department of Statistics and Biostatistics, Rutgers University, Piscataway, NJ, USA.
30
Carolina Center for Genome Sciences, Chapel Hill, NC, USA.

Abstract

BACKGROUND/OBJECTIVES:

Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (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 single-nucleotide polymorphisms (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.

PMID:
27867202
PMCID:
PMC5296276
DOI:
10.1038/ijo.2016.207
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Authors declare no conflict of interest

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