Asthma and lower airway diseaseA genome-wide association study on African-ancestry populations for asthma
Section snippets
Sample description
We analyzed 498 asthmatic cases and 500 nonasthmatic control subjects from the Baltimore–Washington, DC, metropolitan area who self-reported as being of African American ethnicity. These subjects comprised the GRAAD consortium and represent 8 separate, National Institutes of Health–funded studies of asthma in pediatric and adult African American populations, plus 1 study on healthy African Americans. Because asthma is often characterized by onset during childhood, there was a deliberate
Results
Admixture analysis revealed ancestry misclassification for 7 of the African American subjects, and 18 subjects from an ethnically mixed family from Barbados were also excluded from subsequent analysis. Additionally, samples were dropped based on quality control analysis of familial relationships (n = 53) and Mendelian inconsistencies (n = 13). Fourteen samples in the African American group and 1 in the African Caribbean group revealed sex discrepancies compared with clinical records. Among all
Discussion
In this article we report the first GWAS for asthma focused on populations of African descent. Using 2 independent sets of samples, an African American case-control group from Baltimore–Washington, DC (n = 935), and 163 African Caribbean families from Barbados (n = 929), we have identified 3 genes as associated with asthma, each of which are biologically relevant to asthma pathology. However, these findings must be interpreted with caution because of limitations of sample size and the
References (64)
- et al.
A second-generation genomewide screen for asthma-susceptibility alleles in a founder population
Am J Hum Genet
(2000) - et al.
Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families
Genomics
(2000) - et al.
A major susceptibility gene for asthma maps to chromosome 14q24
Am J Hum Genet
(2002) - et al.
Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations
Genomics
(1996) - et al.
Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study
J Allergy Clin Immunol
(2005) - et al.
Patterns and predictors of asthma related emergency department use
Chest
(2001) - et al.
Whole-genome genotyping
Methods Enzymol
(2006) - et al.
PLINK: a tool set for whole-genome association and population-based linkage analyses
Am J Hum Genet
(2007) - et al.
Improved inference of relationship for pairs of individuals
Am J Hum Genet
(2000) - et al.
Case-control association testing with related individuals: a more powerful quasi-likelihood score test
Am J Hum Genet
(2007)
Genome-wide search for atopy susceptibility genes in Dutch families with asthma
J Allergy Clin Immunol
Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor. The gene for which is located on human chromosome 5
J Biol Chem
Alpha1 adrenergic receptors activate phosphatidylinositol 3-kinase in human vascular smooth muscle cells. Role in mitogenesis
J Biol Chem
Cellular isoform of the scrapie agent protein participates in lymphocyte activation
Cell
The cellular prion protein (PrPC) prevents apoptotic neuronal cell death and mitochondrial dysfunction induced by serum deprivation
Brain Res Mol Brain Res
The expression and potential function of cellular prion protein in human lymphocytes
Cell Immunol
PRNP contains both intronic and upstream regulatory regions that may influence susceptibility to Creutzfeldt-Jakob Disease
Gene
DPP10 modulates Kv4-mediated A-type potassium channels
J Biol Chem
Transmembrane interaction mediates complex formation between peptidase homologues and Kv4 channels
Mol Cell Neurosci
Shifting paradigm of association studies: value of rare single-nucleotide polymorphisms
Am J Hum Genet
ORMDL3 variants associated with asthma susceptibility in North Americans of European ancestry
J Allergy Clin Immunol
National surveillance for asthma—United States, 1980-2004
MMWR Surveill Summ
A genome-wide search for quantitative trait loci underlying asthma
Nature
The Collaborative Study on the Genetics of Asthma: a genome-wide search for asthma susceptibility loci in ethnically diverse populations
Nat Genet
Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma
Hum Mol Genet
Candidate genes and a genome-wide search in Italian families with atopic asthmatic children
Clin Exp Allergy
A genome-wide search for linkage to asthma. German Asthma Genetics Group
Genomics
Genome screen for asthma and related phenotypes in the French EGEA study
Am J Respir Crit Care Med
A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population
Nat Genet
Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness
Nature
Genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma
Nature
Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function
N Engl J Med
Cited by (0)
Supported by National Institutes of Health grants HL087699, HL49612, AI50024, AI44840, HL075417, HL072433, AI41040, ES09606, HL072433, and RR03048 and US Environmental Protection Agency grant 83213901, and NIGMS grant S06GM08015. The genome-wide genotyping of the European study was funded by the Wellcome Trust, the Medical Research Council, the French Ministry of Higher Education and Research, the German Ministry of Education and Research (BMBF), the National Genome Research Network (NGFN), the National Institutes of Health (National Human Genome Research Institute and National Heart, Lung, and Blood Institute; G. R. A.), and the European Commission as part of GABRIEL (a multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community). K. C. B. was supported in part by the Mary Beryl Patch Turnbull Scholar Program. R. A. M. was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.
Disclosure of potential conflict of interest: R. A. Mathias, L. Gao, P. Gao, C. M. Ongaco, K. N. Hetrick, K. F. Doheny, E. W. Pugh, A. F. Scott I. Ruczinski, T. H. Beaty, and K. C. Barnes have received research support from the National Institutes of Health. N. N. Hansel has received research support from Pfizer. N. F. Adkinson has equity ownership in AllerQuest LLC, has received research support from the National Institutes of Health, and has provided expert testimony on the topic of drug hypersensitivity. M. C. Liu is a consultant for the Novartis Advisory Board and has received research support from Pfizer, Centocor, and Novartis. J. Ford is a consultant for GlaxoSmithKline and has received research support from the National Institutes of Health and the Centers for Medicare and Medicaid Services. B. A. Raby is the Section Editor for Up to Date and is an in-house lecturer for Novartis Pharmaceuticals. S. T. Weiss has received research support from Genentech. M. Kabesch has financial arrangements with Roxall, Glaxo Wellcome, Novartis, Sanofi Aventis, and Allergopharma and has received research support from DFG, BMBF, and the European Union. G. Abecasis has received research support from GlaxoSmithKline and the National Institutes of Health. The rest of the authors have declared they have no conflict of interest.