Generalization of adiposity genetic loci to US Hispanic women

M. Graff, L. Fernández-Rhodes, S. Liu, C. Carlson, S. Wassertheil-Smoller, M. Neuhouser, A. Reiner, C. Kooperberg, E. Rampersaud, J. E. Manson, L. H. Kuller, B. V. Howard, H. M. Ochs-Balcom, Karen Johnson, M. Z. Vitolins, L. Sucheston, K. Monda, K. E. North

Research output: Contribution to journalArticle

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Abstract

BACKGROUND:Obesity is a public health concern. Yet the identification of adiposity-related genetic variants among United States (US) Hispanics, which is the largest US minority group, remains largely unknown.OBJECTIVE:To interrogate an a priori list of 47 (32 overall body mass and 15 central adiposity) index single-nucleotide polymorphisms (SNPs) previously studied in individuals of European descent among 3494 US Hispanic women in the Women's Health Initiative SNP Health Association Resource (WHI SHARe).DESIGN:Cross-sectional analysis of measured body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were inverse normally transformed after adjusting for age, smoking, center and global ancestry. WC and WHR models were also adjusted for BMI. Genotyping was performed using the Affymetrix 6.0 array. In the absence of an a priori selected SNP, a proxy was selected (r 2 ≥0.8 in CEU).RESULTS:Six BMI loci (TMEM18, NUDT3/HMGA1, FAIM2, FTO, MC4R and KCTD15) and two WC/WHR loci (VEGFA and ITPR2-SSPN) were nominally significant (P<0.05) at the index or proxy SNP in the corresponding BMI and WC/WHR models. To account for distinct linkage disequilibrium patterns in Hispanics and further assess generalization of genetic effects at each locus, we interrogated the evidence for association at the 47 surrounding loci within 1 Mb region of the index or proxy SNP. Three additional BMI loci (FANCL, TFAP2B and ETV5) and five WC/WHR loci (DNM3-PIGC, GRB14, ADAMTS9, LY86 and MSRA) displayed Bonferroni-corrected significant associations with BMI and WC/WHR. Conditional analyses of each index SNP (or its proxy) and the most significant SNP within the 1 Mb region supported the possible presence of index-independent signals at each of these eight loci as well as at KCTD15.CONCLUSION:This study provides evidence for the generalization of nine BMI and seven central adiposity loci in Hispanic women. This study expands the current knowledge of common adiposity-related genetic loci to Hispanic women.

Original languageEnglish (US)
Article numbere85
JournalNutrition and Diabetes
Volume3
Issue numberAUGUST
DOIs
StatePublished - Sep 10 2013

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Genetic Loci
Adiposity
Waist-Hip Ratio
Hispanic Americans
Waist Circumference
Single Nucleotide Polymorphism
Body Mass Index
Proxy
Minority Groups
Health Resources
Linkage Disequilibrium
Women's Health
Public Health
Obesity
Cross-Sectional Studies
Smoking

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Graff, M., Fernández-Rhodes, L., Liu, S., Carlson, C., Wassertheil-Smoller, S., Neuhouser, M., ... North, K. E. (2013). Generalization of adiposity genetic loci to US Hispanic women. Nutrition and Diabetes, 3(AUGUST), [e85]. https://doi.org/10.1038/nutd.2013.26

Generalization of adiposity genetic loci to US Hispanic women. / Graff, M.; Fernández-Rhodes, L.; Liu, S.; Carlson, C.; Wassertheil-Smoller, S.; Neuhouser, M.; Reiner, A.; Kooperberg, C.; Rampersaud, E.; Manson, J. E.; Kuller, L. H.; Howard, B. V.; Ochs-Balcom, H. M.; Johnson, Karen; Vitolins, M. Z.; Sucheston, L.; Monda, K.; North, K. E.

In: Nutrition and Diabetes, Vol. 3, No. AUGUST, e85, 10.09.2013.

Research output: Contribution to journalArticle

Graff, M, Fernández-Rhodes, L, Liu, S, Carlson, C, Wassertheil-Smoller, S, Neuhouser, M, Reiner, A, Kooperberg, C, Rampersaud, E, Manson, JE, Kuller, LH, Howard, BV, Ochs-Balcom, HM, Johnson, K, Vitolins, MZ, Sucheston, L, Monda, K & North, KE 2013, 'Generalization of adiposity genetic loci to US Hispanic women', Nutrition and Diabetes, vol. 3, no. AUGUST, e85. https://doi.org/10.1038/nutd.2013.26
Graff M, Fernández-Rhodes L, Liu S, Carlson C, Wassertheil-Smoller S, Neuhouser M et al. Generalization of adiposity genetic loci to US Hispanic women. Nutrition and Diabetes. 2013 Sep 10;3(AUGUST). e85. https://doi.org/10.1038/nutd.2013.26
Graff, M. ; Fernández-Rhodes, L. ; Liu, S. ; Carlson, C. ; Wassertheil-Smoller, S. ; Neuhouser, M. ; Reiner, A. ; Kooperberg, C. ; Rampersaud, E. ; Manson, J. E. ; Kuller, L. H. ; Howard, B. V. ; Ochs-Balcom, H. M. ; Johnson, Karen ; Vitolins, M. Z. ; Sucheston, L. ; Monda, K. ; North, K. E. / Generalization of adiposity genetic loci to US Hispanic women. In: Nutrition and Diabetes. 2013 ; Vol. 3, No. AUGUST.
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abstract = "BACKGROUND:Obesity is a public health concern. Yet the identification of adiposity-related genetic variants among United States (US) Hispanics, which is the largest US minority group, remains largely unknown.OBJECTIVE:To interrogate an a priori list of 47 (32 overall body mass and 15 central adiposity) index single-nucleotide polymorphisms (SNPs) previously studied in individuals of European descent among 3494 US Hispanic women in the Women's Health Initiative SNP Health Association Resource (WHI SHARe).DESIGN:Cross-sectional analysis of measured body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were inverse normally transformed after adjusting for age, smoking, center and global ancestry. WC and WHR models were also adjusted for BMI. Genotyping was performed using the Affymetrix 6.0 array. In the absence of an a priori selected SNP, a proxy was selected (r 2 ≥0.8 in CEU).RESULTS:Six BMI loci (TMEM18, NUDT3/HMGA1, FAIM2, FTO, MC4R and KCTD15) and two WC/WHR loci (VEGFA and ITPR2-SSPN) were nominally significant (P<0.05) at the index or proxy SNP in the corresponding BMI and WC/WHR models. To account for distinct linkage disequilibrium patterns in Hispanics and further assess generalization of genetic effects at each locus, we interrogated the evidence for association at the 47 surrounding loci within 1 Mb region of the index or proxy SNP. Three additional BMI loci (FANCL, TFAP2B and ETV5) and five WC/WHR loci (DNM3-PIGC, GRB14, ADAMTS9, LY86 and MSRA) displayed Bonferroni-corrected significant associations with BMI and WC/WHR. Conditional analyses of each index SNP (or its proxy) and the most significant SNP within the 1 Mb region supported the possible presence of index-independent signals at each of these eight loci as well as at KCTD15.CONCLUSION:This study provides evidence for the generalization of nine BMI and seven central adiposity loci in Hispanic women. This study expands the current knowledge of common adiposity-related genetic loci to Hispanic women.",
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AU - Graff, M.

AU - Fernández-Rhodes, L.

AU - Liu, S.

AU - Carlson, C.

AU - Wassertheil-Smoller, S.

AU - Neuhouser, M.

AU - Reiner, A.

AU - Kooperberg, C.

AU - Rampersaud, E.

AU - Manson, J. E.

AU - Kuller, L. H.

AU - Howard, B. V.

AU - Ochs-Balcom, H. M.

AU - Johnson, Karen

AU - Vitolins, M. Z.

AU - Sucheston, L.

AU - Monda, K.

AU - North, K. E.

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N2 - BACKGROUND:Obesity is a public health concern. Yet the identification of adiposity-related genetic variants among United States (US) Hispanics, which is the largest US minority group, remains largely unknown.OBJECTIVE:To interrogate an a priori list of 47 (32 overall body mass and 15 central adiposity) index single-nucleotide polymorphisms (SNPs) previously studied in individuals of European descent among 3494 US Hispanic women in the Women's Health Initiative SNP Health Association Resource (WHI SHARe).DESIGN:Cross-sectional analysis of measured body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were inverse normally transformed after adjusting for age, smoking, center and global ancestry. WC and WHR models were also adjusted for BMI. Genotyping was performed using the Affymetrix 6.0 array. In the absence of an a priori selected SNP, a proxy was selected (r 2 ≥0.8 in CEU).RESULTS:Six BMI loci (TMEM18, NUDT3/HMGA1, FAIM2, FTO, MC4R and KCTD15) and two WC/WHR loci (VEGFA and ITPR2-SSPN) were nominally significant (P<0.05) at the index or proxy SNP in the corresponding BMI and WC/WHR models. To account for distinct linkage disequilibrium patterns in Hispanics and further assess generalization of genetic effects at each locus, we interrogated the evidence for association at the 47 surrounding loci within 1 Mb region of the index or proxy SNP. Three additional BMI loci (FANCL, TFAP2B and ETV5) and five WC/WHR loci (DNM3-PIGC, GRB14, ADAMTS9, LY86 and MSRA) displayed Bonferroni-corrected significant associations with BMI and WC/WHR. Conditional analyses of each index SNP (or its proxy) and the most significant SNP within the 1 Mb region supported the possible presence of index-independent signals at each of these eight loci as well as at KCTD15.CONCLUSION:This study provides evidence for the generalization of nine BMI and seven central adiposity loci in Hispanic women. This study expands the current knowledge of common adiposity-related genetic loci to Hispanic women.

AB - BACKGROUND:Obesity is a public health concern. Yet the identification of adiposity-related genetic variants among United States (US) Hispanics, which is the largest US minority group, remains largely unknown.OBJECTIVE:To interrogate an a priori list of 47 (32 overall body mass and 15 central adiposity) index single-nucleotide polymorphisms (SNPs) previously studied in individuals of European descent among 3494 US Hispanic women in the Women's Health Initiative SNP Health Association Resource (WHI SHARe).DESIGN:Cross-sectional analysis of measured body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were inverse normally transformed after adjusting for age, smoking, center and global ancestry. WC and WHR models were also adjusted for BMI. Genotyping was performed using the Affymetrix 6.0 array. In the absence of an a priori selected SNP, a proxy was selected (r 2 ≥0.8 in CEU).RESULTS:Six BMI loci (TMEM18, NUDT3/HMGA1, FAIM2, FTO, MC4R and KCTD15) and two WC/WHR loci (VEGFA and ITPR2-SSPN) were nominally significant (P<0.05) at the index or proxy SNP in the corresponding BMI and WC/WHR models. To account for distinct linkage disequilibrium patterns in Hispanics and further assess generalization of genetic effects at each locus, we interrogated the evidence for association at the 47 surrounding loci within 1 Mb region of the index or proxy SNP. Three additional BMI loci (FANCL, TFAP2B and ETV5) and five WC/WHR loci (DNM3-PIGC, GRB14, ADAMTS9, LY86 and MSRA) displayed Bonferroni-corrected significant associations with BMI and WC/WHR. Conditional analyses of each index SNP (or its proxy) and the most significant SNP within the 1 Mb region supported the possible presence of index-independent signals at each of these eight loci as well as at KCTD15.CONCLUSION:This study provides evidence for the generalization of nine BMI and seven central adiposity loci in Hispanic women. This study expands the current knowledge of common adiposity-related genetic loci to Hispanic women.

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