Asthma genetics and genomics 2009

Current Opinion in Genetics and Development

Volumn 19, Issue 3, 2009, Pages 279-282

  Weiss, Scott T ^a   Raby, Benjamin A ^a   Rogers, Angela ^a  

^a CHANNING LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUTATHIONE TRANSFERASE P1; INTERLEUKIN 4; TUMOR NECROSIS FACTOR ALPHA;

ASTHMA; GENE IDENTIFICATION; GENE LINKAGE DISEQUILIBRIUM; GENE MAPPING; GENETIC ASSOCIATION; GENETIC EPISTASIS; GENETIC LINKAGE; HERITABILITY; HUMAN; HUMAN GENOME; PHENOTYPIC VARIATION; PRIORITY JOURNAL; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM;

ASTHMA; EPIGENESIS, GENETIC; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; GENOME, HUMAN; GENOME-WIDE ASSOCIATION STUDY; HUMANS; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 68649111398     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.gde.2009.05.001     Document Type: Review

References (5)

1. Nielsen D.M., Suchindran S., and Smith C.P. Does strong linkage disequilibrium guarantee redundant association results?. Genet Epidemiol 32 6 (2008) 546-552. This article explains how, with linkage disequilbrium that is similar, but not exactly identical, in two different populations you get lack of replication of results. In addition to different clinical phenotypes, and different environmental exposures this is a major reason for lack of replication in genetic association studies.
2. Rogers A.J., Raby B.A., Lasky-Su J., Murphy A., Lazarus R., Klanderman B.J., Sylvia J.S., Ziniti J.P., Lange C., Celedon J.C., et al. Assessing the reproducibility of asthma candidate gene associations using genome-wide data. Am J Respir Crit Care Med (2009) [epub ahead of print]. This paper provides an explanation for why GWAS genotyping is not adequate to look at candidate genes. It also provides a comprehensive summary of genetic association studies in asthma and all of the references to replication results for the genes identified in the supplementary table of this review.
3. Moffatt M.F., Kabesch M., Liang L., Dixon A.L., Strachan D., Heath S., Depner M., von Berg A., Bufe A., Rietschel E., et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448 7152 (2007) 470-473 [epub 2007 July 4]. This paper is the first asthma GWAS study ever published. It is worth reading for its methods alone.
4. Weedon M.N., Lango H., Lindgren C.M., Wallace C., Evans D.M., Mangino M., Freathy R.M., Perry J.R., Stevens S., Hall A.S., et al. Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet 40 5 (2008) 575-583. This paper has excited a great deal of discussion in the scientific literature about the cause of the missing variation. These authors found 20 replicated height SNPS from GWAS and put them in a regression model and could only explain 3.8% of the variability of height a phenotype known to be highly heritable. This has sparked controversy as to know the reason for the missing variability. As described above my hypothesis is that this is due to the inability to model the epistasis directly.
5. Hao K., Schadt E.E., and Storey J.D. Calibrating the performance of SNP arrays for whole-genome association studies. PLoS Genet 4 6 (2008) e1000109. This paper demonstrates that the current estimates of genome coverage from GWAS chips is overestimated and probably these chips only cover about 60% of the genome not 80-90%.