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-QuirosJinghua 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 D. Martinez, Frank D. Gilliland, L. Keoki Williams, Esteban G. Burchard, Scott T. Weiss, Dan L. Nicolae, Carole Ober*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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)1294-1301
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume130
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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