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

J. Gong; K. K. Nishimura; L. 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; 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

doi:10.1038/ijo.2017.304

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

J. Gong, K. K. Nishimura, L. 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. BostonH. 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

Epidemiology & Population Health

Research output: Contribution to journal › Article

2 Scopus citations

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 language	English (US)
Pages (from-to)	384-390
Number of pages	7
Journal	International Journal of Obesity
Volume	42
Issue number	3
DOIs	https://doi.org/10.1038/ijo.2017.304
State	Published - Mar 1 2018

ASJC Scopus subject areas

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

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Gong, J., Nishimura, K. K., Fernandez-Rhodes, L., 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., ... Peters, U. (2018). Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI. International Journal of Obesity, 42(3), 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, L.; 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 journal › Article

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

Gong, J. ; Nishimura, K. K. ; Fernandez-Rhodes, L. ; 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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title = "Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI",

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 L. 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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doi = "10.1038/ijo.2017.304",

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

AU - Gong, J.

AU - Nishimura, K. K.

AU - Fernandez-Rhodes, L.

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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