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

Ching Ti Liu, Keri L. Monda, Kira C. Taylor, Leslie Lange, Ellen W. Demerath, Walter Palmas, Mary K. Wojczynski, Jaclyn C. Ellis, Mara Z. Vitolins, Simin Liu, George J. Papanicolaou, Marguerite R. Irvin, Luting Xue, Paula J. Griffin, Michael A. Nalls, Adebowale Adeyemo, Jiankang Liu, Guo Li, Edward A. Ruiz-Narvaez, Wei Min ChenFang Chen, Brian E. Henderson, Robert C. Millikan, Christine B. Ambrosone, Sara S. Strom, Xiuqing Guo, Jeanette S. Andrews, Yan V. Sun, Thomas H. Mosley, Lisa R. Yanek, Daniel Shriner, Talin Haritunians, Jerome I. Rotter, Elizabeth K. Speliotes, Megan Smith, Lynn Rosenberg, Josyf Mychaleckyj, Uma Nayak, Ida Spruill, W. Timothy Garvey, Curtis Pettaway, Sarah Nyante, Elisa V. Bandera, Angela F. Britton, Alan B. Zonderman, Laura J. Rasmussen-Torvik, Yii Der Ida Chen, Jingzhong Ding, Kurt Lohman, Stephen B. Kritchevsky, Wei Zhao, Patricia A. Peyser, Sharon L.R. Kardia, Edmond Kabagambe, Ulrich Broeckel, Guanjie Chen, Jie Zhou, Sylvia Wassertheil-Smoller, Marian L. Neuhouser, Evadnie Rampersaud, Bruce Psaty, Charles Kooperberg, Jo Ann E. Manson, Lewis H. Kuller, Heather M. Ochs-Balcom, Karen Johnson, Lara Sucheston, Jose M. Ordovas, Julie R. Palmer, Christopher A. Haiman, Barbara McKnight, Barbara V. Howard, Diane M. Becker, Lawrence F. Bielak, Yongmei Liu, Matthew A. Allison, Struan F.A. Grant, Gregory L. Burke, Sanjay R. Patel, Pamela J. Schreiner, Ingrid B. Borecki, Michele K. Evans, Herman Taylor, Michele M. Sale, Virginia Howard, Christopher S. Carlson, Charles N. Rotimi, Mary Cushman, Tamara B. Harris, Alexander P. Reiner, L. Adrienne Cupples, Kari E. North, Caroline S. Fox

Research output: Contribution to journalArticle

73 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1003681
JournalPLoS genetics
Volume9
Issue number8
DOIs
StatePublished - Aug 1 2013

Fingerprint

Body Fat Distribution
body fat distribution
Waist-Hip Ratio
ancestry
fat
Waist Circumference
genome
waist
Genome
loci
hips
waist circumference
Fats
Population
Single Nucleotide Polymorphism
Genome-Wide Association Study
HDL Cholesterol
Fasting
Insulin
genomics

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Liu, C. T., Monda, K. L., Taylor, K. C., Lange, L., Demerath, E. W., Palmas, W., ... Fox, C. S. (2013). Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci. PLoS genetics, 9(8), [e1003681]. https://doi.org/10.1371/journal.pgen.1003681

Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci. / Liu, Ching Ti; Monda, Keri L.; Taylor, Kira C.; Lange, Leslie; Demerath, Ellen W.; Palmas, Walter; Wojczynski, Mary K.; Ellis, Jaclyn C.; Vitolins, Mara Z.; Liu, Simin; Papanicolaou, George J.; Irvin, Marguerite R.; Xue, Luting; Griffin, Paula J.; Nalls, Michael A.; Adeyemo, Adebowale; Liu, Jiankang; Li, Guo; Ruiz-Narvaez, Edward A.; Chen, Wei Min; Chen, Fang; Henderson, Brian E.; Millikan, Robert C.; Ambrosone, Christine B.; Strom, Sara S.; Guo, Xiuqing; Andrews, Jeanette S.; Sun, Yan V.; Mosley, Thomas H.; Yanek, Lisa R.; Shriner, Daniel; Haritunians, Talin; Rotter, Jerome I.; Speliotes, Elizabeth K.; Smith, Megan; Rosenberg, Lynn; Mychaleckyj, Josyf; Nayak, Uma; Spruill, Ida; Garvey, W. Timothy; Pettaway, Curtis; Nyante, Sarah; Bandera, Elisa V.; Britton, Angela F.; Zonderman, Alan B.; Rasmussen-Torvik, Laura J.; Chen, Yii Der Ida; Ding, Jingzhong; Lohman, Kurt; Kritchevsky, Stephen B.; Zhao, Wei; Peyser, Patricia A.; Kardia, Sharon L.R.; Kabagambe, Edmond; Broeckel, Ulrich; Chen, Guanjie; Zhou, Jie; Wassertheil-Smoller, Sylvia; Neuhouser, Marian L.; Rampersaud, Evadnie; Psaty, Bruce; Kooperberg, Charles; Manson, Jo Ann E.; Kuller, Lewis H.; Ochs-Balcom, Heather M.; Johnson, Karen; Sucheston, Lara; Ordovas, Jose M.; Palmer, Julie R.; Haiman, Christopher A.; McKnight, Barbara; Howard, Barbara V.; Becker, Diane M.; Bielak, Lawrence F.; Liu, Yongmei; Allison, Matthew A.; Grant, Struan F.A.; Burke, Gregory L.; Patel, Sanjay R.; Schreiner, Pamela J.; Borecki, Ingrid B.; Evans, Michele K.; Taylor, Herman; Sale, Michele M.; Howard, Virginia; Carlson, Christopher S.; Rotimi, Charles N.; Cushman, Mary; Harris, Tamara B.; Reiner, Alexander P.; Cupples, L. Adrienne; North, Kari E.; Fox, Caroline S.

In: PLoS genetics, Vol. 9, No. 8, e1003681, 01.08.2013.

Research output: Contribution to journalArticle

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, Ochs-Balcom, HM, Johnson, K, 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 2013, 'Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci', PLoS genetics, vol. 9, no. 8, e1003681. https://doi.org/10.1371/journal.pgen.1003681
Liu, Ching Ti ; Monda, Keri L. ; Taylor, Kira C. ; Lange, Leslie ; Demerath, Ellen W. ; Palmas, Walter ; Wojczynski, Mary K. ; Ellis, Jaclyn C. ; Vitolins, Mara Z. ; Liu, Simin ; Papanicolaou, George J. ; Irvin, Marguerite R. ; Xue, Luting ; Griffin, Paula J. ; Nalls, Michael A. ; Adeyemo, Adebowale ; Liu, Jiankang ; Li, Guo ; Ruiz-Narvaez, Edward A. ; Chen, Wei Min ; Chen, Fang ; Henderson, Brian E. ; Millikan, Robert C. ; Ambrosone, Christine B. ; Strom, Sara S. ; Guo, Xiuqing ; Andrews, Jeanette S. ; Sun, Yan V. ; Mosley, Thomas H. ; Yanek, Lisa R. ; Shriner, Daniel ; Haritunians, Talin ; Rotter, Jerome I. ; Speliotes, Elizabeth K. ; Smith, Megan ; Rosenberg, Lynn ; Mychaleckyj, Josyf ; Nayak, Uma ; Spruill, Ida ; Garvey, W. Timothy ; Pettaway, Curtis ; Nyante, Sarah ; Bandera, Elisa V. ; Britton, Angela F. ; Zonderman, Alan B. ; Rasmussen-Torvik, Laura J. ; Chen, Yii Der Ida ; Ding, Jingzhong ; Lohman, Kurt ; Kritchevsky, Stephen B. ; Zhao, Wei ; Peyser, Patricia A. ; Kardia, Sharon L.R. ; Kabagambe, Edmond ; Broeckel, Ulrich ; Chen, Guanjie ; Zhou, Jie ; Wassertheil-Smoller, Sylvia ; Neuhouser, Marian L. ; Rampersaud, Evadnie ; Psaty, Bruce ; Kooperberg, Charles ; Manson, Jo Ann E. ; Kuller, Lewis H. ; Ochs-Balcom, Heather M. ; Johnson, Karen ; Sucheston, Lara ; Ordovas, Jose M. ; Palmer, Julie R. ; Haiman, Christopher A. ; McKnight, Barbara ; Howard, Barbara V. ; Becker, Diane M. ; Bielak, Lawrence F. ; Liu, Yongmei ; Allison, Matthew A. ; Grant, Struan F.A. ; Burke, Gregory L. ; Patel, Sanjay R. ; Schreiner, Pamela J. ; Borecki, Ingrid B. ; Evans, Michele K. ; Taylor, Herman ; Sale, Michele M. ; Howard, Virginia ; Carlson, Christopher S. ; Rotimi, Charles N. ; Cushman, Mary ; Harris, Tamara B. ; Reiner, Alexander P. ; Cupples, L. Adrienne ; North, Kari E. ; Fox, Caroline S. / Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci. In: PLoS genetics. 2013 ; Vol. 9, No. 8.
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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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TY - JOUR

T1 - Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

AU - Liu, Ching Ti

AU - Monda, Keri L.

AU - Taylor, Kira C.

AU - Lange, Leslie

AU - Demerath, Ellen W.

AU - Palmas, Walter

AU - Wojczynski, Mary K.

AU - Ellis, Jaclyn C.

AU - Vitolins, Mara Z.

AU - Liu, Simin

AU - Papanicolaou, George J.

AU - Irvin, Marguerite R.

AU - Xue, Luting

AU - Griffin, Paula J.

AU - Nalls, Michael A.

AU - Adeyemo, Adebowale

AU - Liu, Jiankang

AU - Li, Guo

AU - Ruiz-Narvaez, Edward A.

AU - Chen, Wei Min

AU - Chen, Fang

AU - Henderson, Brian E.

AU - Millikan, Robert C.

AU - Ambrosone, Christine B.

AU - Strom, Sara S.

AU - Guo, Xiuqing

AU - Andrews, Jeanette S.

AU - Sun, Yan V.

AU - Mosley, Thomas H.

AU - Yanek, Lisa R.

AU - Shriner, Daniel

AU - Haritunians, Talin

AU - Rotter, Jerome I.

AU - Speliotes, Elizabeth K.

AU - Smith, Megan

AU - Rosenberg, Lynn

AU - Mychaleckyj, Josyf

AU - Nayak, Uma

AU - Spruill, Ida

AU - Garvey, W. Timothy

AU - Pettaway, Curtis

AU - Nyante, Sarah

AU - Bandera, Elisa V.

AU - Britton, Angela F.

AU - Zonderman, Alan B.

AU - Rasmussen-Torvik, Laura J.

AU - Chen, Yii Der Ida

AU - Ding, Jingzhong

AU - Lohman, Kurt

AU - Kritchevsky, Stephen B.

AU - Zhao, Wei

AU - Peyser, Patricia A.

AU - Kardia, Sharon L.R.

AU - Kabagambe, Edmond

AU - Broeckel, Ulrich

AU - Chen, Guanjie

AU - Zhou, Jie

AU - Wassertheil-Smoller, Sylvia

AU - Neuhouser, Marian L.

AU - Rampersaud, Evadnie

AU - Psaty, Bruce

AU - Kooperberg, Charles

AU - Manson, Jo Ann E.

AU - Kuller, Lewis H.

AU - Ochs-Balcom, Heather M.

AU - Johnson, Karen

AU - Sucheston, Lara

AU - Ordovas, Jose M.

AU - Palmer, Julie R.

AU - Haiman, Christopher A.

AU - McKnight, Barbara

AU - Howard, Barbara V.

AU - Becker, Diane M.

AU - Bielak, Lawrence F.

AU - Liu, Yongmei

AU - Allison, Matthew A.

AU - Grant, Struan F.A.

AU - Burke, Gregory L.

AU - Patel, Sanjay R.

AU - Schreiner, Pamela J.

AU - Borecki, Ingrid B.

AU - Evans, Michele K.

AU - Taylor, Herman

AU - Sale, Michele M.

AU - Howard, Virginia

AU - Carlson, Christopher S.

AU - Rotimi, Charles N.

AU - Cushman, Mary

AU - Harris, Tamara B.

AU - Reiner, Alexander P.

AU - Cupples, L. Adrienne

AU - North, Kari E.

AU - Fox, Caroline S.

PY - 2013/8/1

Y1 - 2013/8/1

N2 - 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.

AB - 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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DO - 10.1371/journal.pgen.1003681

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