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

S. Yoneyama, J. Yao, X. Guo, L. Fernandez-Rhodes, U. Lim, J. Boston, P. Buzková, C. S. Carlson, I. Cheng, B. Cochran, R. Cooper, G. Ehret, M. Fornage, J. Gong, M. Gross, C. C. Gu, J. Haessler, C. A. Haiman, B. Henderson, L. A. Hindorff & 30 others D. Houston, M. R. Irvin, R. Jackson, L. Kuller, M. Leppert, C. E. Lewis, R. Li, L. Le Marchand, T. C. Matise, K. Dh Nguyen, A. Chakravarti, J. S. Pankow, N. Pankratz, L. Pooler, M. D. Ritchie, S. A. Bien, C. L. Wassel, Y. Di Chen, K. D. Taylor, M. Allison, J. I. Rotter, P. J. Schreiner, F. Schumacher, L. Wilkens, E. Boerwinkle, C. Kooperberg, U. Peters, S. Buyske, M. Graff, K. E. North

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)324-331
Number of pages8
JournalInternational Journal of Obesity
Volume41
Issue number2
DOIs
StatePublished - Feb 1 2017

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Waist-Hip Ratio
Adiposity
Single Nucleotide Polymorphism
Population
Waist Circumference
Meta-Analysis
Body Fat Distribution
Abdominal Fat
Linkage Disequilibrium
Genomics
Epidemiology
Body Mass Index

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations. / Yoneyama, S.; Yao, J.; Guo, X.; Fernandez-Rhodes, L.; Lim, U.; Boston, J.; Buzková, P.; Carlson, C. S.; Cheng, I.; Cochran, B.; Cooper, R.; Ehret, G.; Fornage, M.; Gong, J.; Gross, M.; Gu, C. C.; Haessler, J.; Haiman, C. A.; Henderson, B.; Hindorff, L. A.; Houston, D.; Irvin, M. R.; Jackson, R.; Kuller, L.; Leppert, M.; Lewis, C. E.; Li, R.; Le Marchand, L.; Matise, T. C.; Nguyen, K. Dh; Chakravarti, A.; Pankow, J. S.; Pankratz, N.; Pooler, L.; Ritchie, M. D.; Bien, S. A.; Wassel, C. L.; Chen, Y. Di; Taylor, K. D.; Allison, M.; Rotter, J. I.; Schreiner, P. J.; Schumacher, F.; Wilkens, L.; Boerwinkle, E.; Kooperberg, C.; Peters, U.; Buyske, S.; Graff, M.; North, K. E.

In: International Journal of Obesity, Vol. 41, No. 2, 01.02.2017, p. 324-331.

Research output: Contribution to journalArticle

Yoneyama, S, Yao, J, Guo, X, Fernandez-Rhodes, L, Lim, U, Boston, J, Buzková, P, Carlson, CS, Cheng, I, Cochran, B, Cooper, R, Ehret, G, Fornage, M, Gong, J, Gross, M, Gu, CC, Haessler, J, Haiman, CA, Henderson, B, Hindorff, LA, Houston, D, Irvin, MR, Jackson, R, Kuller, L, Leppert, M, Lewis, CE, Li, R, Le Marchand, L, Matise, TC, Nguyen, KD, Chakravarti, A, Pankow, JS, Pankratz, N, Pooler, L, Ritchie, MD, Bien, SA, Wassel, CL, Chen, YD, Taylor, KD, Allison, M, Rotter, JI, Schreiner, PJ, Schumacher, F, Wilkens, L, Boerwinkle, E, Kooperberg, C, Peters, U, Buyske, S, Graff, M & North, KE 2017, 'Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations', International Journal of Obesity, vol. 41, no. 2, pp. 324-331. https://doi.org/10.1038/ijo.2016.207
Yoneyama, S. ; Yao, J. ; Guo, X. ; Fernandez-Rhodes, L. ; Lim, U. ; Boston, J. ; Buzková, P. ; Carlson, C. S. ; Cheng, I. ; Cochran, B. ; Cooper, R. ; Ehret, G. ; Fornage, M. ; Gong, J. ; Gross, M. ; Gu, C. C. ; Haessler, J. ; Haiman, C. A. ; Henderson, B. ; Hindorff, L. A. ; Houston, D. ; Irvin, M. R. ; Jackson, R. ; Kuller, L. ; Leppert, M. ; Lewis, C. E. ; Li, R. ; Le Marchand, L. ; Matise, T. C. ; Nguyen, K. Dh ; Chakravarti, A. ; Pankow, J. S. ; Pankratz, N. ; Pooler, L. ; Ritchie, M. D. ; Bien, S. A. ; Wassel, C. L. ; Chen, Y. Di ; Taylor, K. D. ; Allison, M. ; Rotter, J. I. ; Schreiner, P. J. ; Schumacher, F. ; Wilkens, L. ; Boerwinkle, E. ; Kooperberg, C. ; Peters, U. ; Buyske, S. ; Graff, M. ; North, K. E. / Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations. In: International Journal of Obesity. 2017 ; Vol. 41, No. 2. pp. 324-331.
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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.",
author = "S. Yoneyama and J. Yao and X. Guo and L. Fernandez-Rhodes and U. Lim and J. Boston and P. Buzkov{\'a} and Carlson, {C. S.} and I. Cheng and B. Cochran and R. Cooper and G. Ehret and M. Fornage and J. Gong and M. Gross and Gu, {C. C.} and J. Haessler and Haiman, {C. A.} and B. Henderson and Hindorff, {L. A.} and D. Houston and Irvin, {M. R.} and R. Jackson and L. Kuller and M. Leppert and Lewis, {C. E.} and R. Li and {Le Marchand}, L. and Matise, {T. C.} and Nguyen, {K. Dh} and A. Chakravarti and Pankow, {J. S.} and N. Pankratz and L. Pooler and Ritchie, {M. D.} and Bien, {S. A.} and Wassel, {C. L.} and Chen, {Y. Di} and Taylor, {K. D.} and M. Allison and Rotter, {J. I.} and Schreiner, {P. J.} and F. Schumacher and L. Wilkens and E. Boerwinkle and C. Kooperberg and U. Peters and S. Buyske and M. Graff and North, {K. E.}",
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TY - JOUR

T1 - Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations

AU - Yoneyama, S.

AU - Yao, J.

AU - Guo, X.

AU - Fernandez-Rhodes, L.

AU - Lim, U.

AU - Boston, J.

AU - Buzková, P.

AU - Carlson, C. S.

AU - Cheng, I.

AU - Cochran, B.

AU - Cooper, R.

AU - Ehret, G.

AU - Fornage, M.

AU - Gong, J.

AU - Gross, M.

AU - Gu, C. C.

AU - Haessler, J.

AU - Haiman, C. A.

AU - Henderson, B.

AU - Hindorff, L. A.

AU - Houston, D.

AU - Irvin, M. R.

AU - Jackson, R.

AU - Kuller, L.

AU - Leppert, M.

AU - Lewis, C. E.

AU - Li, R.

AU - Le Marchand, L.

AU - Matise, T. C.

AU - Nguyen, K. Dh

AU - Chakravarti, A.

AU - Pankow, J. S.

AU - Pankratz, N.

AU - Pooler, L.

AU - Ritchie, M. D.

AU - Bien, S. A.

AU - Wassel, C. L.

AU - Chen, Y. Di

AU - Taylor, K. D.

AU - Allison, M.

AU - Rotter, J. I.

AU - Schreiner, P. J.

AU - Schumacher, F.

AU - Wilkens, L.

AU - Boerwinkle, E.

AU - Kooperberg, C.

AU - Peters, U.

AU - Buyske, S.

AU - Graff, M.

AU - North, K. E.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

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DO - 10.1038/ijo.2016.207

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JO - International Journal of Obesity

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