Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

Liu, CT and Monda, KL and Taylor, KC and Lange, L and Demerath, EW and Palmas, W and Wojczynski, MK and Ellis, JC and Vitolins, MZ and Liu, S and Papanicolaou, GJ and Irvin, MR and Xue, L and Griffin, PJ and Nalls, MA and Adeyemo, A and Liu, J and Li, G and Ruiz-Narvaez, EA and Chen, WM and Chen, F and Henderson, BE and Millikan, RC and Ambrosone, CB and Strom, SS and Guo, X and Andrews, JS and Sun, YV and Mosley, TH and Yanek, LR and Shriner, D and Haritunians, T and Rotter, JI and Speliotes, EK and Smith, M and Rosenberg, L and Mychaleckyj, J and Nayak, U and Spruill, I and Garvey, WT and Pettaway, C and Nyante, S and Bandera, EV and Britton, AF and Zonderman, AB and Rasmussen-Torvik, LJ and Chen, YDI and Ding, J and Lohman, K and Kritchevsky, SB and Zhao, W and Peyser, PA and Kardia, SLR and Kabagambe, E and Broeckel, U and Chen, G and Zhou, J and Wassertheil-Smoller, S and Neuhouser, ML and Rampersaud, E and Psaty, B and Kooperberg, C and Manson, JAE and Kuller, LH and Ochs-Balcom, HM and Johnson, KC and Sucheston, L and Ordovas, JM and Palmer, JR and Haiman, CA and McKnight, B and Howard, BV and Becker, DM and Bielak, LF and Liu, Y and Allison, MA and Grant, SFA and Burke, GL and Patel, SR and Schreiner, PJ and Borecki, IB and Evans, MK and Taylor, H and Sale, MM and Howard, V and Carlson, CS and Rotimi, CN and Cushman, M and Harris, TB and Reiner, AP and Cupples, LA and North, KE and Fox, CS (2013) Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci. PLoS Genetics, 9 (8). ISSN 1553-7390

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Abstract

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10-6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10-8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10-8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10-8; RREB1: p = 5.7×10-8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.

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Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Liu, CT Monda, KL Taylor, KC Lange, L Demerath, EW Palmas, W Wojczynski, MK Ellis, JC Vitolins, MZ Liu, S Papanicolaou, GJ Irvin, MR Xue, L Griffin, PJ Nalls, MA Adeyemo, A Liu, J Li, G Ruiz-Narvaez, EA Chen, WM Chen, F Henderson, BE Millikan, RC Ambrosone, CB Strom, SS Guo, X Andrews, JS Sun, YV Mosley, TH Yanek, LR Shriner, D Haritunians, T Rotter, JI Speliotes, EK Smith, M Rosenberg, L Mychaleckyj, J Nayak, U Spruill, I Garvey, WT Pettaway, C Nyante, S Bandera, EV Britton, AF Zonderman, AB Rasmussen-Torvik, LJ Chen, YDI Ding, J Lohman, K Kritchevsky, SB Zhao, W Peyser, PA Kardia, SLR Kabagambe, E Broeckel, U Chen, G Zhou, J Wassertheil-Smoller, S Neuhouser, ML Rampersaud, E Psaty, B Kooperberg, C Manson, JAE Kuller, LH kuller@pitt.edu KULLER Ochs-Balcom, HM Johnson, KC Sucheston, L Ordovas, JM Palmer, JR Haiman, CA McKnight, B Howard, BV Becker, DM Bielak, LF Liu, Y Allison, MA Grant, SFA Burke, GL Patel, SR Schreiner, PJ Borecki, IB Evans, MK Taylor, H Sale, MM Howard, V Carlson, CS Rotimi, CN Cushman, M Harris, TB Reiner, AP Cupples, LA North, KE Fox, CS
Date:	1 August 2013
Date Type:	Publication
Journal or Publication Title:	PLoS Genetics
Volume:	9
Number:	8
DOI or Unique Handle:	10.1371/journal.pgen.1003681
Schools and Programs:	School of Public Health > Epidemiology
Refereed:	Yes
ISSN:	1553-7390
Date Deposited:	23 Sep 2013 17:21
Last Modified:	02 Nov 2022 11:55
URI:	http://d-scholarship.pitt.edu/id/eprint/19774

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