Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans

Rachel A. Myers, Blanca E. Himes, Christopher R. Gignoux, James J. Yang, W. James Gauderman, Cristina Rebordosa, Jianming Xie, Dara G. Torgerson, Albert M. Levin, James Baurley, Penelope E. Graves, Rasika A. Mathias, Isabelle Romieu, Lindsey A. Roth, David Conti, Lydiana Avila, Celeste Eng, Hita Vora, Michael A. Lenoir, Manuel Soto-Quiros & 24 others Jinghua Liu, Juan C. Celedón, Harold J. Farber, Rajesh Kumar, Pedro C. Avila, Kelley Meade, Denise Serebrisky, Shannon Thyne, William Rodriguez-Cintron, Jose R. Rodriguez-Santana, Luisa N. Borrell, Robert F. Lemanske, Eugene R. Bleecker, Deborah A. Meyers, Stephanie J. London, Kathleen C. Barnes, Benjamin A. Raby, Fernando Martinez, Frank D. Gilliland, L. Keoki Williams, Esteban G. Burchard, Scott T. Weiss, Dan L. Nicolae, Carole Ober

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk. Objectives: We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis. Methods: We selected 3186 single nucleotide polymorphisms for replication based on the P values from the EVE Consortium meta-analysis. These single nucleotide polymorphisms were genotyped in ethnically diverse replication samples from 9 different studies, totaling 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study, and the resulting test statistics were combined in a meta-analysis. Results: Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined odds ratio = 1.18; 95% CI, 1.10-1.25) and rs9570077 (combined odds ratio =1.20; 95% CI, 1.12-1.29) on chromosome 13q21. We could not replicate any additional associations in the African Americans or Latinos. Conclusions: This extended replication study identified 2 additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latinos highlights the difficulty in replicating associations in admixed populations.

Original languageEnglish (US)
Pages (from-to)1295-1301
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume130
Issue number6
DOIs
StatePublished - Dec 2012

Fingerprint

Meta-Analysis
Asthma
Hispanic Americans
African Americans
Single Nucleotide Polymorphism
Odds Ratio
Chromosomes, Human, Pair 19
Genome-Wide Association Study
Population
Chromosomes
Genes

Keywords

  • Asthma
  • genetic risk factors
  • KLK3
  • meta-analysis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Myers, R. A., Himes, B. E., Gignoux, C. R., Yang, J. J., Gauderman, W. J., Rebordosa, C., ... Ober, C. (2012). Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans. Journal of Allergy and Clinical Immunology, 130(6), 1295-1301. https://doi.org/10.1016/j.jaci.2012.07.054

Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans. / Myers, Rachel A.; Himes, Blanca E.; Gignoux, Christopher R.; Yang, James J.; Gauderman, W. James; Rebordosa, Cristina; Xie, Jianming; Torgerson, Dara G.; Levin, Albert M.; Baurley, James; Graves, Penelope E.; Mathias, Rasika A.; Romieu, Isabelle; Roth, Lindsey A.; Conti, David; Avila, Lydiana; Eng, Celeste; Vora, Hita; Lenoir, Michael A.; Soto-Quiros, Manuel; Liu, Jinghua; Celedón, Juan C.; Farber, Harold J.; Kumar, Rajesh; Avila, Pedro C.; Meade, Kelley; Serebrisky, Denise; Thyne, Shannon; Rodriguez-Cintron, William; Rodriguez-Santana, Jose R.; Borrell, Luisa N.; Lemanske, Robert F.; Bleecker, Eugene R.; Meyers, Deborah A.; London, Stephanie J.; Barnes, Kathleen C.; Raby, Benjamin A.; Martinez, Fernando; Gilliland, Frank D.; Williams, L. Keoki; Burchard, Esteban G.; Weiss, Scott T.; Nicolae, Dan L.; Ober, Carole.

In: Journal of Allergy and Clinical Immunology, Vol. 130, No. 6, 12.2012, p. 1295-1301.

Research output: Contribution to journalArticle

Myers, RA, Himes, BE, Gignoux, CR, Yang, JJ, Gauderman, WJ, Rebordosa, C, Xie, J, Torgerson, DG, Levin, AM, Baurley, J, Graves, PE, Mathias, RA, Romieu, I, Roth, LA, Conti, D, Avila, L, Eng, C, Vora, H, Lenoir, MA, Soto-Quiros, M, Liu, J, Celedón, JC, Farber, HJ, Kumar, R, Avila, PC, Meade, K, Serebrisky, D, Thyne, S, Rodriguez-Cintron, W, Rodriguez-Santana, JR, Borrell, LN, Lemanske, RF, Bleecker, ER, Meyers, DA, London, SJ, Barnes, KC, Raby, BA, Martinez, F, Gilliland, FD, Williams, LK, Burchard, EG, Weiss, ST, Nicolae, DL & Ober, C 2012, 'Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans', Journal of Allergy and Clinical Immunology, vol. 130, no. 6, pp. 1295-1301. https://doi.org/10.1016/j.jaci.2012.07.054
Myers, Rachel A. ; Himes, Blanca E. ; Gignoux, Christopher R. ; Yang, James J. ; Gauderman, W. James ; Rebordosa, Cristina ; Xie, Jianming ; Torgerson, Dara G. ; Levin, Albert M. ; Baurley, James ; Graves, Penelope E. ; Mathias, Rasika A. ; Romieu, Isabelle ; Roth, Lindsey A. ; Conti, David ; Avila, Lydiana ; Eng, Celeste ; Vora, Hita ; Lenoir, Michael A. ; Soto-Quiros, Manuel ; Liu, Jinghua ; Celedón, Juan C. ; Farber, Harold J. ; Kumar, Rajesh ; Avila, Pedro C. ; Meade, Kelley ; Serebrisky, Denise ; Thyne, Shannon ; Rodriguez-Cintron, William ; Rodriguez-Santana, Jose R. ; Borrell, Luisa N. ; Lemanske, Robert F. ; Bleecker, Eugene R. ; Meyers, Deborah A. ; London, Stephanie J. ; Barnes, Kathleen C. ; Raby, Benjamin A. ; Martinez, Fernando ; Gilliland, Frank D. ; Williams, L. Keoki ; Burchard, Esteban G. ; Weiss, Scott T. ; Nicolae, Dan L. ; Ober, Carole. / Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans. In: Journal of Allergy and Clinical Immunology. 2012 ; Vol. 130, No. 6. pp. 1295-1301.
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abstract = "Background: Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk. Objectives: We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis. Methods: We selected 3186 single nucleotide polymorphisms for replication based on the P values from the EVE Consortium meta-analysis. These single nucleotide polymorphisms were genotyped in ethnically diverse replication samples from 9 different studies, totaling 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study, and the resulting test statistics were combined in a meta-analysis. Results: Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined odds ratio = 1.18; 95{\%} CI, 1.10-1.25) and rs9570077 (combined odds ratio =1.20; 95{\%} CI, 1.12-1.29) on chromosome 13q21. We could not replicate any additional associations in the African Americans or Latinos. Conclusions: This extended replication study identified 2 additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latinos highlights the difficulty in replicating associations in admixed populations.",
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author = "Myers, {Rachel A.} and Himes, {Blanca E.} and Gignoux, {Christopher R.} and Yang, {James J.} and Gauderman, {W. James} and Cristina Rebordosa and Jianming Xie and Torgerson, {Dara G.} and Levin, {Albert M.} and James Baurley and Graves, {Penelope E.} and Mathias, {Rasika A.} and Isabelle Romieu and Roth, {Lindsey A.} and David Conti and Lydiana Avila and Celeste Eng and Hita Vora and Lenoir, {Michael A.} and Manuel Soto-Quiros and Jinghua Liu and Celed{\'o}n, {Juan C.} and Farber, {Harold J.} and Rajesh Kumar and Avila, {Pedro C.} and Kelley Meade and Denise Serebrisky and Shannon Thyne and William Rodriguez-Cintron and Rodriguez-Santana, {Jose R.} and Borrell, {Luisa N.} and Lemanske, {Robert F.} and Bleecker, {Eugene R.} and Meyers, {Deborah A.} and London, {Stephanie J.} and Barnes, {Kathleen C.} and Raby, {Benjamin A.} and Fernando Martinez and Gilliland, {Frank D.} and Williams, {L. Keoki} and Burchard, {Esteban G.} and Weiss, {Scott T.} and Nicolae, {Dan L.} and Carole Ober",
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T1 - Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans

AU - Myers, Rachel A.

AU - Himes, Blanca E.

AU - Gignoux, Christopher R.

AU - Yang, James J.

AU - Gauderman, W. James

AU - Rebordosa, Cristina

AU - Xie, Jianming

AU - Torgerson, Dara G.

AU - Levin, Albert M.

AU - Baurley, James

AU - Graves, Penelope E.

AU - Mathias, Rasika A.

AU - Romieu, Isabelle

AU - Roth, Lindsey A.

AU - Conti, David

AU - Avila, Lydiana

AU - Eng, Celeste

AU - Vora, Hita

AU - Lenoir, Michael A.

AU - Soto-Quiros, Manuel

AU - Liu, Jinghua

AU - Celedón, Juan C.

AU - Farber, Harold J.

AU - Kumar, Rajesh

AU - Avila, Pedro C.

AU - Meade, Kelley

AU - Serebrisky, Denise

AU - Thyne, Shannon

AU - Rodriguez-Cintron, William

AU - Rodriguez-Santana, Jose R.

AU - Borrell, Luisa N.

AU - Lemanske, Robert F.

AU - Bleecker, Eugene R.

AU - Meyers, Deborah A.

AU - London, Stephanie J.

AU - Barnes, Kathleen C.

AU - Raby, Benjamin A.

AU - Martinez, Fernando

AU - Gilliland, Frank D.

AU - Williams, L. Keoki

AU - Burchard, Esteban G.

AU - Weiss, Scott T.

AU - Nicolae, Dan L.

AU - Ober, Carole

PY - 2012/12

Y1 - 2012/12

N2 - Background: Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk. Objectives: We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis. Methods: We selected 3186 single nucleotide polymorphisms for replication based on the P values from the EVE Consortium meta-analysis. These single nucleotide polymorphisms were genotyped in ethnically diverse replication samples from 9 different studies, totaling 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study, and the resulting test statistics were combined in a meta-analysis. Results: Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined odds ratio = 1.18; 95% CI, 1.10-1.25) and rs9570077 (combined odds ratio =1.20; 95% CI, 1.12-1.29) on chromosome 13q21. We could not replicate any additional associations in the African Americans or Latinos. Conclusions: This extended replication study identified 2 additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latinos highlights the difficulty in replicating associations in admixed populations.

AB - Background: Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk. Objectives: We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis. Methods: We selected 3186 single nucleotide polymorphisms for replication based on the P values from the EVE Consortium meta-analysis. These single nucleotide polymorphisms were genotyped in ethnically diverse replication samples from 9 different studies, totaling 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study, and the resulting test statistics were combined in a meta-analysis. Results: Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined odds ratio = 1.18; 95% CI, 1.10-1.25) and rs9570077 (combined odds ratio =1.20; 95% CI, 1.12-1.29) on chromosome 13q21. We could not replicate any additional associations in the African Americans or Latinos. Conclusions: This extended replication study identified 2 additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latinos highlights the difficulty in replicating associations in admixed populations.

KW - Asthma

KW - genetic risk factors

KW - KLK3

KW - meta-analysis

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JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

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