Replication and fine mapping of asthma-associated loci in individuals of African ancestry

David B. Kantor, Cameron D. Palmer, Taylor R. Young, Yan Meng, Zofia K. Gajdos, Helen Lyon, Alkes L. Price, Samuela Pollack, Stephanie J. London, Laura R. Loehr, Lewis J Smith, Rajesh Kumar, David R. Jacobs, Marcy F. Petrini, George T. O'Connor, Wendy B. White, George Papanicolaou, Kristin M. Burkart, Susan R. Heckbert, R. Graham Barr & 1 others Joel N. Hirschhorn*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.

Original languageEnglish (US)
Pages (from-to)1039-1047
Number of pages9
JournalHuman Genetics
Volume132
Issue number9
DOIs
StatePublished - Sep 1 2013

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Asthma
African Americans
Population
Ethnic Groups
Single Nucleotide Polymorphism
Interleukin-13
Genome-Wide Association Study
Linkage Disequilibrium
Genome
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Kantor, D. B., Palmer, C. D., Young, T. R., Meng, Y., Gajdos, Z. K., Lyon, H., ... Hirschhorn, J. N. (2013). Replication and fine mapping of asthma-associated loci in individuals of African ancestry. Human Genetics, 132(9), 1039-1047. https://doi.org/10.1007/s00439-013-1310-7
Kantor, David B. ; Palmer, Cameron D. ; Young, Taylor R. ; Meng, Yan ; Gajdos, Zofia K. ; Lyon, Helen ; Price, Alkes L. ; Pollack, Samuela ; London, Stephanie J. ; Loehr, Laura R. ; Smith, Lewis J ; Kumar, Rajesh ; Jacobs, David R. ; Petrini, Marcy F. ; O'Connor, George T. ; White, Wendy B. ; Papanicolaou, George ; Burkart, Kristin M. ; Heckbert, Susan R. ; Barr, R. Graham ; Hirschhorn, Joel N. / Replication and fine mapping of asthma-associated loci in individuals of African ancestry. In: Human Genetics. 2013 ; Vol. 132, No. 9. pp. 1039-1047.
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Kantor, DB, Palmer, CD, Young, TR, Meng, Y, Gajdos, ZK, Lyon, H, Price, AL, Pollack, S, London, SJ, Loehr, LR, Smith, LJ, Kumar, R, Jacobs, DR, Petrini, MF, O'Connor, GT, White, WB, Papanicolaou, G, Burkart, KM, Heckbert, SR, Barr, RG & Hirschhorn, JN 2013, 'Replication and fine mapping of asthma-associated loci in individuals of African ancestry', Human Genetics, vol. 132, no. 9, pp. 1039-1047. https://doi.org/10.1007/s00439-013-1310-7

Replication and fine mapping of asthma-associated loci in individuals of African ancestry. / Kantor, David B.; Palmer, Cameron D.; Young, Taylor R.; Meng, Yan; Gajdos, Zofia K.; Lyon, Helen; Price, Alkes L.; Pollack, Samuela; London, Stephanie J.; Loehr, Laura R.; Smith, Lewis J; Kumar, Rajesh; Jacobs, David R.; Petrini, Marcy F.; O'Connor, George T.; White, Wendy B.; Papanicolaou, George; Burkart, Kristin M.; Heckbert, Susan R.; Barr, R. Graham; Hirschhorn, Joel N.

In: Human Genetics, Vol. 132, No. 9, 01.09.2013, p. 1039-1047.

Research output: Contribution to journalArticle

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AU - Kantor, David B.

AU - Palmer, Cameron D.

AU - Young, Taylor R.

AU - Meng, Yan

AU - Gajdos, Zofia K.

AU - Lyon, Helen

AU - Price, Alkes L.

AU - Pollack, Samuela

AU - London, Stephanie J.

AU - Loehr, Laura R.

AU - Smith, Lewis J

AU - Kumar, Rajesh

AU - Jacobs, David R.

AU - Petrini, Marcy F.

AU - O'Connor, George T.

AU - White, Wendy B.

AU - Papanicolaou, George

AU - Burkart, Kristin M.

AU - Heckbert, Susan R.

AU - Barr, R. Graham

AU - Hirschhorn, Joel N.

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.

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Kantor DB, Palmer CD, Young TR, Meng Y, Gajdos ZK, Lyon H et al. Replication and fine mapping of asthma-associated loci in individuals of African ancestry. Human Genetics. 2013 Sep 1;132(9):1039-1047. https://doi.org/10.1007/s00439-013-1310-7