The EVE Consortium

To identify asthma-susceptibility genes in ethnically diverse populations

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EVE is a consortium comprised of U.S. investigators who have conducted genome-wide association studies (GWAS) of asthma and whose main objective is to conduct a meta-analysis to identify asthma-susceptibility loci. The consortium includes investigators at 9 U.S. institutions with GWAS results for more than 15,000 individuals representing European American, African American, U.S. Hispanic, and Mexican populations.

We recently received American Recovery and Reinvestment Act (ARRA grant RC2 HL101651 ) funding from the NIH for the EVE investigators to replicate the most significant meta-analysis results in more than 15,000 asthma cases and controls of European Americans, African Americans, and U.S. Hispanics, to study additional phenotypes and to develop methods for meta-analysis.

Participating Sites

InstitutionPrincipal Investigator(s)
University of Chicago (Coordinating Center)Carole Ober, PhD, Dan Nicolae, PhD
Harvard Medical SchoolScott Weiss, MD, Benjamin Raby, MD
Henry Ford Health SystemKeoki Williams, MD, MPH
Johns Hopkins UniversityKathleen Barnes, PhD
NIEHS Stephanie J. London, MD, PhD
University of ArizonaFernando Martinez, MD
University of California, San Francisco Esteban Gonzalez Burchard, MD, MPH
University of Southern California Frank Gilliland, MD, PhD, Jim Gauderman, PhD
Wake Forest University Deborah Meyers, PhD, Eugene Bleecker, MD
Program Officer: Susan Banks-Schlegel, PhD (NHLBI)

Study Aims

Aim 1: Replicate associations with ~1500 SNPs that show independent associations with asthma in one or more ethnic groups in previously collected samples housed in the laboratories of the EVE investigators.

Aim 2: Conduct additional meta-analysis in the samples that have undergone the GWAS, including studies of i) asthma-associated biomarkers that have been measured in these samples, ii) associations with copy number polymorphisms (CNPs), iii) genome-wide genotype-by-sex, genotype-by-environment and gene-by-gene interaction effects on asthma.

Aim 3: Develop methods that combine data from different types of study samples for the meta-analyses and integrate network and pathway analyses into our approaches to gene discovery.

 

EVE Publications

Lead Investigator(s) Article
Nicolae, Ober  Torgerson DG et al. (2011) Meta-Analysis of Genome-Wide Association Studies of Asthma in Ethnically Diverse North American Populations. Nat Genet. 43(9): 887-92. PMID: 21804549 PMCID: 3445408
Nicolae, Ober  Myers RA et al. (2012) Further Replication Studies of the EVE Consortium Meta-Analysis Identifies 2 Asthma Risk Loci in European Americans. J Allergy Clin Immunol. 130(6): 1294-301. Epub 2012 Oct 4. PMID: 23040885 PMCID: 3666859
Weiss  Himes BE et al. (2013) Integration of Mouse and Human Genome-Wide Association Data Identifies KCNIP4 as an Asthma Gene. PLoS One 8(2): e56179. Epub 2013 Feb 14. PMID: 23457522 PMCID: 3572953
Barnes, Williams  Levin AM, Mathias RA et al. (2013) A Meta-Analysis of Genome-Wide Association Studies for Serum Total IgE in Diverse Study Populations. J Allergy Clin Immunol. 131(4), 1176-84. Epub 2012 Nov 10. PMID: 23146381 PMCID: 3596497
Nicolae, Ober  Myers RA et al. (2014) Genome-Wide Interaction Studies Reveal Sex-Specific Asthma Risk Alleles. Hum Mol Genet. 23(19), 5251-9. Epub 2014 May 13. PMID: 24824216
Raby, Weiss  Sharma S, Zhou X et al. (2014) A Genome-Wide Survey of CD4 Lymphocyte Regulatory Genetic Variants Identifies Novel Asthma Genes. J Allergy Clin Immunol. 134(5), 1153-62. Epub 2014 Jun 13. PMID: 24934276
Nicolae, Ober  Igartua C et al. (2015) Ethnic-Specific Associations of Rare and Low-Frequency DNA Sequence Variants with Asthma. Nat Commun. 6:5965. 2015 Jan 16. PMID: 25591454 PMCID: 4309441

 

GWAS included in Meta-analysis

A. Case-Control Samples
Investigator(s) Sample Platform #Cases/
Controls
Age Asthma Definition Other Phenotypes
European Americans
Bleecker, Meyers STAMPEED Illumina 1M 742/382 14% children MD dx + sx + meds + reversibility and/or BHR PFT, IgE, skin tests
Gilliland, Gauderman CHS Illumina 550k 643/959 children Self-report PFT (50%), evironmental exposures
Ober STAMPEED Illumina 1M 101/198 57% children MD dx + sx + meds + reversibility and/or BHR PFT, ETS, UTS, IgE, skin tests
Total Eur. American Cases and Controls 1486/1539
African Americans
Barnes GRAAD Illumina 650Y 464/471 32% children MD dx + sx + meds + reversibility and/or BHR PFT, IgE, skin tests
Bleecker, Meyers STAMPEED Illumina 1M 355/270 29% children MD dx + sx + meds + reversibility and/or BHR PFT, IgE, skin tests
Ober STAMPEED Illumina 1M 186/181 45% children MD dx + sx + meds + reversibility and/or BHR PFT, ETS, UTS, IgE, skin tests, eos
Williams SAPPHIRE Affymetrix 6.0 149/132 19% children MD dx + sx + meds + reversibility and/or BHR PFT, medication, environmental exposures
Total Afr. American Cases and Controls 1154/1054
Hispanics
Gilliland, Gauderman CHS Illumina 550k 606/792 children Self-report PFT (50%), evironmental exposures
Total Hispanic Cases and Controls 606/792



B. Trios
Investigator Sample Platform #Trios Age Asthma Definition Other Phenotypes
European Americans
Martinez CARE Affymetrix 6.0 217 children MD dx + sx + meds + reversibility and/or BHR PFT, skin tests, IgE, eos, FeNO
Weiss CAMP Affymetrix 6.0 422 children MD dx + sx + meds + reversibility and/or BHR PFT, skin tests, IgE, ETS, UTS, eos
Total European American Trios 639
African Americans
Barnes Barbados Illumina 650Y 413 32% children MD dx + sx + meds + reversibility and/or BHR PFT, IgE, skin tests, eos
Total African American Trios 413
Hispanics
Burchard GALA1 Affymetrix 6.0 588 children MD dx + sx + meds + reversibility and/or BHR PFT, skin tests, IgE, ETS, air pollution
London MCCAS Illumina 550K 492 children MD dx + sx + meds skin tests, ETS, air pollution
Martinez CARE Affymetrix 6.0 52 children MD dx + sx + meds + reversibility and/or BHR PFT, skin tests, IgE, eos, FeNO
Total Hispanic Trios 1132

Published GWAS by EVE Investigators

 
Lead Investigator(s) Article
Burchard Choudhry S, Taub M et al. (2008) Genome-Wide Screen for Asthma in Puerto Ricans: Evidence for Association with 5q23 Region. Hum Genet. 123(5):455-468. Epub 2008 Apr 10. PMID: 18401594 PMCID: 2664533
London  Hancock DB et al. (2009) Genome-Wide Association Study Implicates Chromosome 9q21.31 as a Susceptibility Locus for Asthma in Mexican Children. PLoS Genet. 5(8):e10000623. Epub 2009 Aug 28. PMID: 19714205 PMCID: 2722731
Raby, Weiss  Himes BE et al. (2009) Genome-Wide Association Analysis Identifies PDE4D as an Asthma-Susceptibility Gene. Am J Hum Genet. 84(5):581-93. Epub 2009 May 7. PMID: 19426955 PMCID: 2681010
Barnes  Mathias RA et al. (2010) A Genome-Wide Association Study on African-Ancestry Populations for Asthma. J Allergy Clin Immunol. 125(2):336-346. Epub 2009 Nov 11. PMID: 19910028 PMCID: 3606015
Bleecker, Meyers Li X, Ampleford EJ et al. (2012) Genome-Wide Association Studies of Asthma Indicate Opposite Immunopathogenesis Direction from Autoimmune Disease. J Allergy Clin Immunol. 130(4):861-8.e7. Epub 2012 Jun 12. PMID: 22694930 PMCID: 3579216
Nicolae, Ober  Torgerson DA et al. (2012) Genome-Wide Ancestry Association Testing Identifies a Common European Variant on 6q14.1 as a Risk Factor for Asthma in African Americans. J Allergy Clin Immunol. 130(3):622-629.e9. Epub 2012 May 18. PMID: 22607992 PMCID: 3503456

Website administered by William Wentworth-Sheilds (wws@uchicago.edu)