Genetic risk factors for BMI and obesity in an ethnically diverse population: Results from the population architecture using genomics and epidemiology (PAGE) study

Megan D. Fesinmeyer, Kari E. North, Marylyn D. Ritchie, Unhee Lim, Nora Franceschini, Lynne R. Wilkens, Myron D. Gross, Petra Bůžková, Kimberly Glenn, P. Miguel Quibrera, Lindsay Fernández-Rhodes, Qiong Li, Jay Fowke, Rongling Li, Christopher S. Carlson, Ross L. Prentice, Lewis H. Kuller, Joann E. Manson, Tara C. Matise, Shelley A. ColeChristina T.L. Chen, Barbara V. Howard, Laurence N. Kolonel, Brian E. Henderson, Kristine R. Monroe, Dana C. Crawford, Lucia A. Hindorff, Steven Buyske, Christopher A. Haiman, Loic Le Marchand, Ulrike Peters

Research output: Contribution to journalArticle

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Abstract

Objective: Several genome-wide association studies (GWAS) have demonstrated that common genetic variants contribute to obesity. However, studies of this complex trait have focused on ancestrally European populations, despite the high prevalence of obesity in some minority groups. Design and Methods: As part of the "Population Architecture using Genomics and Epidemiology (PAGE)" Consortium, we investigated the association between 13 GWAS-identified single-nucleotide polymorphisms (SNPs) and BMI and obesity in 69,775 subjects, including 6,149 American Indians, 15,415 African-Americans, 2,438 East Asians, 7,346 Hispanics, 604 Pacific Islanders, and 37,823 European Americans. For the BMI-increasing allele of each SNP, we calculated β coefficients using linear regression (for BMI) and risk estimates using logistic regression (for obesity defined as BMI ≥ 30) followed by fixed-effects meta-analysis to combine results across PAGE sites. Analyses stratified by racial/ethnic group assumed an additive genetic model and were adjusted for age, sex, and current smoking. We defined "replicating SNPs" (in European Americans) and "generalizing SNPs" (in other racial/ethnic groups) as those associated with an allele frequency-specific increase in BMI. Results: By this definition, we replicated 9/13 SNP associations (5 out of 8 loci) in European Americans. We also generalized 8/13 SNP associations (5/8 loci) in East Asians, 7/13 (5/8 loci) in African Americans, 6/13 (4/8 loci) in Hispanics, 5/8 in Pacific Islanders (5/8 loci), and 5/9 (4/8 loci) in American Indians. Conclusion: Linkage disequilibrium patterns suggest that tagSNPs selected for European Americans may not adequately tag causal variants in other ancestry groups. Accordingly, fine-mapping in large samples is needed to comprehensively explore these loci in diverse populations.

Original languageEnglish (US)
Pages (from-to)835-846
Number of pages12
JournalObesity
Volume21
Issue number4
DOIs
StatePublished - Jan 1 2013

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Genomics
Single Nucleotide Polymorphism
Epidemiology
Obesity
Population
North American Indians
Genome-Wide Association Study
Hispanic Americans
Ethnic Groups
African Americans
Minority Groups
Genetic Models
Linkage Disequilibrium
Gene Frequency
Meta-Analysis
Linear Models
Logistic Models
Smoking
Alleles

All Science Journal Classification (ASJC) codes

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

Cite this

Genetic risk factors for BMI and obesity in an ethnically diverse population : Results from the population architecture using genomics and epidemiology (PAGE) study. / Fesinmeyer, Megan D.; North, Kari E.; Ritchie, Marylyn D.; Lim, Unhee; Franceschini, Nora; Wilkens, Lynne R.; Gross, Myron D.; Bůžková, Petra; Glenn, Kimberly; Quibrera, P. Miguel; Fernández-Rhodes, Lindsay; Li, Qiong; Fowke, Jay; Li, Rongling; Carlson, Christopher S.; Prentice, Ross L.; Kuller, Lewis H.; Manson, Joann E.; Matise, Tara C.; Cole, Shelley A.; Chen, Christina T.L.; Howard, Barbara V.; Kolonel, Laurence N.; Henderson, Brian E.; Monroe, Kristine R.; Crawford, Dana C.; Hindorff, Lucia A.; Buyske, Steven; Haiman, Christopher A.; Le Marchand, Loic; Peters, Ulrike.

In: Obesity, Vol. 21, No. 4, 01.01.2013, p. 835-846.

Research output: Contribution to journalArticle

Fesinmeyer, MD, North, KE, Ritchie, MD, Lim, U, Franceschini, N, Wilkens, LR, Gross, MD, Bůžková, P, Glenn, K, Quibrera, PM, Fernández-Rhodes, L, Li, Q, Fowke, J, Li, R, Carlson, CS, Prentice, RL, Kuller, LH, Manson, JE, Matise, TC, Cole, SA, Chen, CTL, Howard, BV, Kolonel, LN, Henderson, BE, Monroe, KR, Crawford, DC, Hindorff, LA, Buyske, S, Haiman, CA, Le Marchand, L & Peters, U 2013, 'Genetic risk factors for BMI and obesity in an ethnically diverse population: Results from the population architecture using genomics and epidemiology (PAGE) study', Obesity, vol. 21, no. 4, pp. 835-846. https://doi.org/10.1002/oby.20268
Fesinmeyer, Megan D. ; North, Kari E. ; Ritchie, Marylyn D. ; Lim, Unhee ; Franceschini, Nora ; Wilkens, Lynne R. ; Gross, Myron D. ; Bůžková, Petra ; Glenn, Kimberly ; Quibrera, P. Miguel ; Fernández-Rhodes, Lindsay ; Li, Qiong ; Fowke, Jay ; Li, Rongling ; Carlson, Christopher S. ; Prentice, Ross L. ; Kuller, Lewis H. ; Manson, Joann E. ; Matise, Tara C. ; Cole, Shelley A. ; Chen, Christina T.L. ; Howard, Barbara V. ; Kolonel, Laurence N. ; Henderson, Brian E. ; Monroe, Kristine R. ; Crawford, Dana C. ; Hindorff, Lucia A. ; Buyske, Steven ; Haiman, Christopher A. ; Le Marchand, Loic ; Peters, Ulrike. / Genetic risk factors for BMI and obesity in an ethnically diverse population : Results from the population architecture using genomics and epidemiology (PAGE) study. In: Obesity. 2013 ; Vol. 21, No. 4. pp. 835-846.
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abstract = "Objective: Several genome-wide association studies (GWAS) have demonstrated that common genetic variants contribute to obesity. However, studies of this complex trait have focused on ancestrally European populations, despite the high prevalence of obesity in some minority groups. Design and Methods: As part of the {"}Population Architecture using Genomics and Epidemiology (PAGE){"} Consortium, we investigated the association between 13 GWAS-identified single-nucleotide polymorphisms (SNPs) and BMI and obesity in 69,775 subjects, including 6,149 American Indians, 15,415 African-Americans, 2,438 East Asians, 7,346 Hispanics, 604 Pacific Islanders, and 37,823 European Americans. For the BMI-increasing allele of each SNP, we calculated β coefficients using linear regression (for BMI) and risk estimates using logistic regression (for obesity defined as BMI ≥ 30) followed by fixed-effects meta-analysis to combine results across PAGE sites. Analyses stratified by racial/ethnic group assumed an additive genetic model and were adjusted for age, sex, and current smoking. We defined {"}replicating SNPs{"} (in European Americans) and {"}generalizing SNPs{"} (in other racial/ethnic groups) as those associated with an allele frequency-specific increase in BMI. Results: By this definition, we replicated 9/13 SNP associations (5 out of 8 loci) in European Americans. We also generalized 8/13 SNP associations (5/8 loci) in East Asians, 7/13 (5/8 loci) in African Americans, 6/13 (4/8 loci) in Hispanics, 5/8 in Pacific Islanders (5/8 loci), and 5/9 (4/8 loci) in American Indians. Conclusion: Linkage disequilibrium patterns suggest that tagSNPs selected for European Americans may not adequately tag causal variants in other ancestry groups. Accordingly, fine-mapping in large samples is needed to comprehensively explore these loci in diverse populations.",
author = "Fesinmeyer, {Megan D.} and North, {Kari E.} and Ritchie, {Marylyn D.} and Unhee Lim and Nora Franceschini and Wilkens, {Lynne R.} and Gross, {Myron D.} and Petra Bůžkov{\'a} and Kimberly Glenn and Quibrera, {P. Miguel} and Lindsay Fern{\'a}ndez-Rhodes and Qiong Li and Jay Fowke and Rongling Li and Carlson, {Christopher S.} and Prentice, {Ross L.} and Kuller, {Lewis H.} and Manson, {Joann E.} and Matise, {Tara C.} and Cole, {Shelley A.} and Chen, {Christina T.L.} and Howard, {Barbara V.} and Kolonel, {Laurence N.} and Henderson, {Brian E.} and Monroe, {Kristine R.} and Crawford, {Dana C.} and Hindorff, {Lucia A.} and Steven Buyske and Haiman, {Christopher A.} and {Le Marchand}, Loic and Ulrike Peters",
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T1 - Genetic risk factors for BMI and obesity in an ethnically diverse population

T2 - Results from the population architecture using genomics and epidemiology (PAGE) study

AU - Fesinmeyer, Megan D.

AU - North, Kari E.

AU - Ritchie, Marylyn D.

AU - Lim, Unhee

AU - Franceschini, Nora

AU - Wilkens, Lynne R.

AU - Gross, Myron D.

AU - Bůžková, Petra

AU - Glenn, Kimberly

AU - Quibrera, P. Miguel

AU - Fernández-Rhodes, Lindsay

AU - Li, Qiong

AU - Fowke, Jay

AU - Li, Rongling

AU - Carlson, Christopher S.

AU - Prentice, Ross L.

AU - Kuller, Lewis H.

AU - Manson, Joann E.

AU - Matise, Tara C.

AU - Cole, Shelley A.

AU - Chen, Christina T.L.

AU - Howard, Barbara V.

AU - Kolonel, Laurence N.

AU - Henderson, Brian E.

AU - Monroe, Kristine R.

AU - Crawford, Dana C.

AU - Hindorff, Lucia A.

AU - Buyske, Steven

AU - Haiman, Christopher A.

AU - Le Marchand, Loic

AU - Peters, Ulrike

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Objective: Several genome-wide association studies (GWAS) have demonstrated that common genetic variants contribute to obesity. However, studies of this complex trait have focused on ancestrally European populations, despite the high prevalence of obesity in some minority groups. Design and Methods: As part of the "Population Architecture using Genomics and Epidemiology (PAGE)" Consortium, we investigated the association between 13 GWAS-identified single-nucleotide polymorphisms (SNPs) and BMI and obesity in 69,775 subjects, including 6,149 American Indians, 15,415 African-Americans, 2,438 East Asians, 7,346 Hispanics, 604 Pacific Islanders, and 37,823 European Americans. For the BMI-increasing allele of each SNP, we calculated β coefficients using linear regression (for BMI) and risk estimates using logistic regression (for obesity defined as BMI ≥ 30) followed by fixed-effects meta-analysis to combine results across PAGE sites. Analyses stratified by racial/ethnic group assumed an additive genetic model and were adjusted for age, sex, and current smoking. We defined "replicating SNPs" (in European Americans) and "generalizing SNPs" (in other racial/ethnic groups) as those associated with an allele frequency-specific increase in BMI. Results: By this definition, we replicated 9/13 SNP associations (5 out of 8 loci) in European Americans. We also generalized 8/13 SNP associations (5/8 loci) in East Asians, 7/13 (5/8 loci) in African Americans, 6/13 (4/8 loci) in Hispanics, 5/8 in Pacific Islanders (5/8 loci), and 5/9 (4/8 loci) in American Indians. Conclusion: Linkage disequilibrium patterns suggest that tagSNPs selected for European Americans may not adequately tag causal variants in other ancestry groups. Accordingly, fine-mapping in large samples is needed to comprehensively explore these loci in diverse populations.

AB - Objective: Several genome-wide association studies (GWAS) have demonstrated that common genetic variants contribute to obesity. However, studies of this complex trait have focused on ancestrally European populations, despite the high prevalence of obesity in some minority groups. Design and Methods: As part of the "Population Architecture using Genomics and Epidemiology (PAGE)" Consortium, we investigated the association between 13 GWAS-identified single-nucleotide polymorphisms (SNPs) and BMI and obesity in 69,775 subjects, including 6,149 American Indians, 15,415 African-Americans, 2,438 East Asians, 7,346 Hispanics, 604 Pacific Islanders, and 37,823 European Americans. For the BMI-increasing allele of each SNP, we calculated β coefficients using linear regression (for BMI) and risk estimates using logistic regression (for obesity defined as BMI ≥ 30) followed by fixed-effects meta-analysis to combine results across PAGE sites. Analyses stratified by racial/ethnic group assumed an additive genetic model and were adjusted for age, sex, and current smoking. We defined "replicating SNPs" (in European Americans) and "generalizing SNPs" (in other racial/ethnic groups) as those associated with an allele frequency-specific increase in BMI. Results: By this definition, we replicated 9/13 SNP associations (5 out of 8 loci) in European Americans. We also generalized 8/13 SNP associations (5/8 loci) in East Asians, 7/13 (5/8 loci) in African Americans, 6/13 (4/8 loci) in Hispanics, 5/8 in Pacific Islanders (5/8 loci), and 5/9 (4/8 loci) in American Indians. Conclusion: Linkage disequilibrium patterns suggest that tagSNPs selected for European Americans may not adequately tag causal variants in other ancestry groups. Accordingly, fine-mapping in large samples is needed to comprehensively explore these loci in diverse populations.

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