The EVE Consortium
To identify asthma-susceptibility genes in ethnically diverse populations
 |
 |
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
| Institution | Principal Investigator(s) |
|---|---|
| University of Chicago (Coordinating Center) | Carole Ober, PhD, Dan Nicolae, PhD |
| Harvard Medical School | Scott Weiss, MD, Benjamin Raby, MD |
| Henry Ford Health System | Keoki Williams, MD, MPH |
| Johns Hopkins University | Kathleen Barnes, PhD |
| NIEHS | Stephanie J. London, MD, PhD |
| University of Arizona | Fernando 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)