Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations

Clara C. Elbers, Yiran Guo, Vinicius Tragante, Erik P A van Iperen, Matthew B. Lanktree, Berta Almoguera Castillo, Fang Chen, Lisa Yanek, Mary K. Wojczynski, Yun R. Li, Bart Ferwerda, Christie M. Ballantyne, Sarah G. Buxbaum, Yii Der Ida Chen, Wei Min Chen, L. Adrienne Cupples, Mary Cushman, Yanan Duan, David Duggan, Michele K. EvansJyotika K. Fernandes, Myriam Fornage, Melissa Garcia, W. Timothy Garvey, Nicole Glazer, Felicia Gomez, Tamara B. Harris, Indrani Halder, Virginia J. Howard, Margaux F. Keller, M. Ilyas Kamboh, Charles Kooperberg, Stephen B. Kritchevsky, Andrea LaCroix, Kiang Liu, Yongmei Liu, Kiran Musunuru, Anne B. Newman, N. Charlotte Onland-Moret, Jose Ordovas, Inga Peter, Wendy S Post, Susan Redline, Steven E. Reis, Richa Saxena, Pamela J. Schreiner, Kelly A. Volcik, Xingbin Wang, Salim Yusuf, Alan B. Zonderland, Sonia S. Anand, Diane M Becker, Bruce Psaty, Daniel J. Rader, Alex P. Reiner, Stephen S. Rich, Jerome I. Rotter, Michèle M. Sale, Michael Y. Tsai, Ingrid B. Borecki, Robert A. Hegele, Sekar Kathiresan, Michael A. Nalls, Herman A. Taylor, Hakon Hakonarson, Suthesh Sivapalaratnam, Folkert W. Asselbergs, Fotios Drenos, James G. Wilson, Brendan J. Keating

Research output: Contribution to journalArticle

Abstract

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ~2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ~50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10-7 and p = 1.5×10-6 respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10-12). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.

Original languageEnglish (US)
Article numbere50198
JournalPLoS One
Volume7
Issue number12
DOIs
StatePublished - Dec 7 2012

Fingerprint

Hispanic Americans
meta-analysis
Meta-Analysis
Genes
Lipids
African Americans
lipids
Population
loci
genes
nationalities and ethnic groups
genotyping
Single Nucleotide Polymorphism
nonsense mutation
Cholesterol
Nonsense Codon
LDL Cholesterol
HDL Cholesterol
low density lipoprotein cholesterol
high density lipoprotein cholesterol

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Elbers, C. C., Guo, Y., Tragante, V., van Iperen, E. P. A., Lanktree, M. B., Castillo, B. A., ... Keating, B. J. (2012). Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations. PLoS One, 7(12), [e50198]. https://doi.org/10.1371/journal.pone.0050198

Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations. / Elbers, Clara C.; Guo, Yiran; Tragante, Vinicius; van Iperen, Erik P A; Lanktree, Matthew B.; Castillo, Berta Almoguera; Chen, Fang; Yanek, Lisa; Wojczynski, Mary K.; Li, Yun R.; Ferwerda, Bart; Ballantyne, Christie M.; Buxbaum, Sarah G.; Chen, Yii Der Ida; Chen, Wei Min; Cupples, L. Adrienne; Cushman, Mary; Duan, Yanan; Duggan, David; Evans, Michele K.; Fernandes, Jyotika K.; Fornage, Myriam; Garcia, Melissa; Garvey, W. Timothy; Glazer, Nicole; Gomez, Felicia; Harris, Tamara B.; Halder, Indrani; Howard, Virginia J.; Keller, Margaux F.; Kamboh, M. Ilyas; Kooperberg, Charles; Kritchevsky, Stephen B.; LaCroix, Andrea; Liu, Kiang; Liu, Yongmei; Musunuru, Kiran; Newman, Anne B.; Onland-Moret, N. Charlotte; Ordovas, Jose; Peter, Inga; Post, Wendy S; Redline, Susan; Reis, Steven E.; Saxena, Richa; Schreiner, Pamela J.; Volcik, Kelly A.; Wang, Xingbin; Yusuf, Salim; Zonderland, Alan B.; Anand, Sonia S.; Becker, Diane M; Psaty, Bruce; Rader, Daniel J.; Reiner, Alex P.; Rich, Stephen S.; Rotter, Jerome I.; Sale, Michèle M.; Tsai, Michael Y.; Borecki, Ingrid B.; Hegele, Robert A.; Kathiresan, Sekar; Nalls, Michael A.; Taylor, Herman A.; Hakonarson, Hakon; Sivapalaratnam, Suthesh; Asselbergs, Folkert W.; Drenos, Fotios; Wilson, James G.; Keating, Brendan J.

In: PLoS One, Vol. 7, No. 12, e50198, 07.12.2012.

Research output: Contribution to journalArticle

Elbers, CC, Guo, Y, Tragante, V, van Iperen, EPA, Lanktree, MB, Castillo, BA, Chen, F, Yanek, L, Wojczynski, MK, Li, YR, Ferwerda, B, Ballantyne, CM, Buxbaum, SG, Chen, YDI, Chen, WM, Cupples, LA, Cushman, M, Duan, Y, Duggan, D, Evans, MK, Fernandes, JK, Fornage, M, Garcia, M, Garvey, WT, Glazer, N, Gomez, F, Harris, TB, Halder, I, Howard, VJ, Keller, MF, Kamboh, MI, Kooperberg, C, Kritchevsky, SB, LaCroix, A, Liu, K, Liu, Y, Musunuru, K, Newman, AB, Onland-Moret, NC, Ordovas, J, Peter, I, Post, WS, Redline, S, Reis, SE, Saxena, R, Schreiner, PJ, Volcik, KA, Wang, X, Yusuf, S, Zonderland, AB, Anand, SS, Becker, DM, Psaty, B, Rader, DJ, Reiner, AP, Rich, SS, Rotter, JI, Sale, MM, Tsai, MY, Borecki, IB, Hegele, RA, Kathiresan, S, Nalls, MA, Taylor, HA, Hakonarson, H, Sivapalaratnam, S, Asselbergs, FW, Drenos, F, Wilson, JG & Keating, BJ 2012, 'Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations', PLoS One, vol. 7, no. 12, e50198. https://doi.org/10.1371/journal.pone.0050198
Elbers CC, Guo Y, Tragante V, van Iperen EPA, Lanktree MB, Castillo BA et al. Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations. PLoS One. 2012 Dec 7;7(12). e50198. https://doi.org/10.1371/journal.pone.0050198
Elbers, Clara C. ; Guo, Yiran ; Tragante, Vinicius ; van Iperen, Erik P A ; Lanktree, Matthew B. ; Castillo, Berta Almoguera ; Chen, Fang ; Yanek, Lisa ; Wojczynski, Mary K. ; Li, Yun R. ; Ferwerda, Bart ; Ballantyne, Christie M. ; Buxbaum, Sarah G. ; Chen, Yii Der Ida ; Chen, Wei Min ; Cupples, L. Adrienne ; Cushman, Mary ; Duan, Yanan ; Duggan, David ; Evans, Michele K. ; Fernandes, Jyotika K. ; Fornage, Myriam ; Garcia, Melissa ; Garvey, W. Timothy ; Glazer, Nicole ; Gomez, Felicia ; Harris, Tamara B. ; Halder, Indrani ; Howard, Virginia J. ; Keller, Margaux F. ; Kamboh, M. Ilyas ; Kooperberg, Charles ; Kritchevsky, Stephen B. ; LaCroix, Andrea ; Liu, Kiang ; Liu, Yongmei ; Musunuru, Kiran ; Newman, Anne B. ; Onland-Moret, N. Charlotte ; Ordovas, Jose ; Peter, Inga ; Post, Wendy S ; Redline, Susan ; Reis, Steven E. ; Saxena, Richa ; Schreiner, Pamela J. ; Volcik, Kelly A. ; Wang, Xingbin ; Yusuf, Salim ; Zonderland, Alan B. ; Anand, Sonia S. ; Becker, Diane M ; Psaty, Bruce ; Rader, Daniel J. ; Reiner, Alex P. ; Rich, Stephen S. ; Rotter, Jerome I. ; Sale, Michèle M. ; Tsai, Michael Y. ; Borecki, Ingrid B. ; Hegele, Robert A. ; Kathiresan, Sekar ; Nalls, Michael A. ; Taylor, Herman A. ; Hakonarson, Hakon ; Sivapalaratnam, Suthesh ; Asselbergs, Folkert W. ; Drenos, Fotios ; Wilson, James G. ; Keating, Brendan J. / Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations. In: PLoS One. 2012 ; Vol. 7, No. 12.
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abstract = "Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ~2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ~50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10-7 and p = 1.5×10-6 respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10-12). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.",
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AU - Elbers, Clara C.

AU - Guo, Yiran

AU - Tragante, Vinicius

AU - van Iperen, Erik P A

AU - Lanktree, Matthew B.

AU - Castillo, Berta Almoguera

AU - Chen, Fang

AU - Yanek, Lisa

AU - Wojczynski, Mary K.

AU - Li, Yun R.

AU - Ferwerda, Bart

AU - Ballantyne, Christie M.

AU - Buxbaum, Sarah G.

AU - Chen, Yii Der Ida

AU - Chen, Wei Min

AU - Cupples, L. Adrienne

AU - Cushman, Mary

AU - Duan, Yanan

AU - Duggan, David

AU - Evans, Michele K.

AU - Fernandes, Jyotika K.

AU - Fornage, Myriam

AU - Garcia, Melissa

AU - Garvey, W. Timothy

AU - Glazer, Nicole

AU - Gomez, Felicia

AU - Harris, Tamara B.

AU - Halder, Indrani

AU - Howard, Virginia J.

AU - Keller, Margaux F.

AU - Kamboh, M. Ilyas

AU - Kooperberg, Charles

AU - Kritchevsky, Stephen B.

AU - LaCroix, Andrea

AU - Liu, Kiang

AU - Liu, Yongmei

AU - Musunuru, Kiran

AU - Newman, Anne B.

AU - Onland-Moret, N. Charlotte

AU - Ordovas, Jose

AU - Peter, Inga

AU - Post, Wendy S

AU - Redline, Susan

AU - Reis, Steven E.

AU - Saxena, Richa

AU - Schreiner, Pamela J.

AU - Volcik, Kelly A.

AU - Wang, Xingbin

AU - Yusuf, Salim

AU - Zonderland, Alan B.

AU - Anand, Sonia S.

AU - Becker, Diane M

AU - Psaty, Bruce

AU - Rader, Daniel J.

AU - Reiner, Alex P.

AU - Rich, Stephen S.

AU - Rotter, Jerome I.

AU - Sale, Michèle M.

AU - Tsai, Michael Y.

AU - Borecki, Ingrid B.

AU - Hegele, Robert A.

AU - Kathiresan, Sekar

AU - Nalls, Michael A.

AU - Taylor, Herman A.

AU - Hakonarson, Hakon

AU - Sivapalaratnam, Suthesh

AU - Asselbergs, Folkert W.

AU - Drenos, Fotios

AU - Wilson, James G.

AU - Keating, Brendan J.

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