Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI

J. Gong, K. K. Nishimura, Lindsay Fernandez-Rhodes, J. Haessler, S. Bien, M. Graff, U. Lim, Y. Lu, M. Gross, M. Fornage, S. Yoneyama, C. R. Isasi, P. Buzkova, M. Daviglus, D. Y. Lin, R. Tao, R. Goodloe, W. S. Bush, E. Farber-Eger, J. Boston & 28 others H. H. Dilks, G. Ehret, C. C. Gu, C. E. Lewis, K. D.H. Nguyen, R. Cooper, M. Leppert, M. R. Irvin, E. P. Bottinger, L. R. Wilkens, C. A. Haiman, L. Park, K. R. Monroe, I. Cheng, D. O. Stram, C. S. Carlson, R. Jackson, L. Kuller, D. Houston, C. Kooperberg, S. Buyske, L. A. Hindorff, D. C. Crawford, R. J.F. Loos, L. Le Marchand, T. C. Matise, K. E. North, U. Peters

Research output: Contribution to journalArticle

Abstract

Objective:Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population.Subjects:Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models.Results:We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 × 10 ' 7). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue.Conclusion:Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations.

Original languageEnglish (US)
Pages (from-to)384-390
Number of pages7
JournalInternational Journal of Obesity
Volume42
Issue number3
DOIs
StatePublished - Mar 1 2018

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Body Mass Index
Population
Single Nucleotide Polymorphism
Meta-Analysis
Oceanic Ancestry Group
Multifactorial Inheritance
North American Indians
Genomics
Computational Biology
Hispanic Americans
African Americans
Adipose Tissue
Linear Models
Epidemiology
Cohort Studies
Obesity
Genome
Health

All Science Journal Classification (ASJC) codes

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

Cite this

Gong, J. ; Nishimura, K. K. ; Fernandez-Rhodes, Lindsay ; Haessler, J. ; Bien, S. ; Graff, M. ; Lim, U. ; Lu, Y. ; Gross, M. ; Fornage, M. ; Yoneyama, S. ; Isasi, C. R. ; Buzkova, P. ; Daviglus, M. ; Lin, D. Y. ; Tao, R. ; Goodloe, R. ; Bush, W. S. ; Farber-Eger, E. ; Boston, J. ; Dilks, H. H. ; Ehret, G. ; Gu, C. C. ; Lewis, C. E. ; Nguyen, K. D.H. ; Cooper, R. ; Leppert, M. ; Irvin, M. R. ; Bottinger, E. P. ; Wilkens, L. R. ; Haiman, C. A. ; Park, L. ; Monroe, K. R. ; Cheng, I. ; Stram, D. O. ; Carlson, C. S. ; Jackson, R. ; Kuller, L. ; Houston, D. ; Kooperberg, C. ; Buyske, S. ; Hindorff, L. A. ; Crawford, D. C. ; Loos, R. J.F. ; Le Marchand, L. ; Matise, T. C. ; North, K. E. ; Peters, U. / Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI. In: International Journal of Obesity. 2018 ; Vol. 42, No. 3. pp. 384-390.
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abstract = "Objective:Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population.Subjects:Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models.Results:We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 × 10 ' 7). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue.Conclusion:Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations.",
author = "J. Gong and Nishimura, {K. K.} and Lindsay Fernandez-Rhodes and J. Haessler and S. Bien and M. Graff and U. Lim and Y. Lu and M. Gross and M. Fornage and S. Yoneyama and Isasi, {C. R.} and P. Buzkova and M. Daviglus and Lin, {D. Y.} and R. Tao and R. Goodloe and Bush, {W. S.} and E. Farber-Eger and J. Boston and Dilks, {H. H.} and G. Ehret and Gu, {C. C.} and Lewis, {C. E.} and Nguyen, {K. D.H.} and R. Cooper and M. Leppert and Irvin, {M. R.} and Bottinger, {E. P.} and Wilkens, {L. R.} and Haiman, {C. A.} and L. Park and Monroe, {K. R.} and I. Cheng and Stram, {D. O.} and Carlson, {C. S.} and R. Jackson and L. Kuller and D. Houston and C. Kooperberg and S. Buyske and Hindorff, {L. A.} and Crawford, {D. C.} and Loos, {R. J.F.} and {Le Marchand}, L. and Matise, {T. C.} and North, {K. E.} and U. Peters",
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Gong, J, Nishimura, KK, Fernandez-Rhodes, L, Haessler, J, Bien, S, Graff, M, Lim, U, Lu, Y, Gross, M, Fornage, M, Yoneyama, S, Isasi, CR, Buzkova, P, Daviglus, M, Lin, DY, Tao, R, Goodloe, R, Bush, WS, Farber-Eger, E, Boston, J, Dilks, HH, Ehret, G, Gu, CC, Lewis, CE, Nguyen, KDH, Cooper, R, Leppert, M, Irvin, MR, Bottinger, EP, Wilkens, LR, Haiman, CA, Park, L, Monroe, KR, Cheng, I, Stram, DO, Carlson, CS, Jackson, R, Kuller, L, Houston, D, Kooperberg, C, Buyske, S, Hindorff, LA, Crawford, DC, Loos, RJF, Le Marchand, L, Matise, TC, North, KE & Peters, U 2018, 'Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI', International Journal of Obesity, vol. 42, no. 3, pp. 384-390. https://doi.org/10.1038/ijo.2017.304

Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI. / Gong, J.; Nishimura, K. K.; Fernandez-Rhodes, Lindsay; Haessler, J.; Bien, S.; Graff, M.; Lim, U.; Lu, Y.; Gross, M.; Fornage, M.; Yoneyama, S.; Isasi, C. R.; Buzkova, P.; Daviglus, M.; Lin, D. Y.; Tao, R.; Goodloe, R.; Bush, W. S.; Farber-Eger, E.; Boston, J.; Dilks, H. H.; Ehret, G.; Gu, C. C.; Lewis, C. E.; Nguyen, K. D.H.; Cooper, R.; Leppert, M.; Irvin, M. R.; Bottinger, E. P.; Wilkens, L. R.; Haiman, C. A.; Park, L.; Monroe, K. R.; Cheng, I.; Stram, D. O.; Carlson, C. S.; Jackson, R.; Kuller, L.; Houston, D.; Kooperberg, C.; Buyske, S.; Hindorff, L. A.; Crawford, D. C.; Loos, R. J.F.; Le Marchand, L.; Matise, T. C.; North, K. E.; Peters, U.

In: International Journal of Obesity, Vol. 42, No. 3, 01.03.2018, p. 384-390.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI

AU - Gong, J.

AU - Nishimura, K. K.

AU - Fernandez-Rhodes, Lindsay

AU - Haessler, J.

AU - Bien, S.

AU - Graff, M.

AU - Lim, U.

AU - Lu, Y.

AU - Gross, M.

AU - Fornage, M.

AU - Yoneyama, S.

AU - Isasi, C. R.

AU - Buzkova, P.

AU - Daviglus, M.

AU - Lin, D. Y.

AU - Tao, R.

AU - Goodloe, R.

AU - Bush, W. S.

AU - Farber-Eger, E.

AU - Boston, J.

AU - Dilks, H. H.

AU - Ehret, G.

AU - Gu, C. C.

AU - Lewis, C. E.

AU - Nguyen, K. D.H.

AU - Cooper, R.

AU - Leppert, M.

AU - Irvin, M. R.

AU - Bottinger, E. P.

AU - Wilkens, L. R.

AU - Haiman, C. A.

AU - Park, L.

AU - Monroe, K. R.

AU - Cheng, I.

AU - Stram, D. O.

AU - Carlson, C. S.

AU - Jackson, R.

AU - Kuller, L.

AU - Houston, D.

AU - Kooperberg, C.

AU - Buyske, S.

AU - Hindorff, L. A.

AU - Crawford, D. C.

AU - Loos, R. J.F.

AU - Le Marchand, L.

AU - Matise, T. C.

AU - North, K. E.

AU - Peters, U.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Objective:Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population.Subjects:Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models.Results:We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 × 10 ' 7). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue.Conclusion:Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations.

AB - Objective:Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population.Subjects:Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models.Results:We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 × 10 ' 7). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue.Conclusion:Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations.

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DO - 10.1038/ijo.2017.304

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EP - 390

JO - International Journal of Obesity

JF - International Journal of Obesity

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