The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Effect of 17q21 Variants and Smoking Exposure in Early-Onset Asthma
Open accessAbstract
BACKGROUND: A genomewide association study has shown an association between variants at chromosome 17q21 and an increased risk of asthma. To elucidate the relationship between this locus and disease, we examined a large, family-based data set that included extensive phenotypic and environmental data from the Epidemiological Study on the Genetics and Environment of Asthma. METHODS: We tested 36 single-nucleotide polymorphisms (SNPs) in the 17q21 region in 1511 subjects from 372 families for an association with asthma. We also tested for genetic heterogeneity according to the age at the onset of asthma and exposure to environmental tobacco smoke in early life. RESULTS: Eleven SNPs were significantly associated with asthma (P<0.01), of which three (rs8069176, rs2305480, and rs4795400) were strongly associated (P<0.001). Ordered-subset regression analysis led us to select an onset at 4 years of age or younger to classify patients as having early-onset asthma. Association with early-onset asthma was highly significant (P<10(-5) for four SNPs), whereas no association was found with late-onset asthma. With respect to exposure to environmental tobacco smoke in early life, we observed a significant association with early-onset asthma only in exposed subjects (P<5x10(-5) for six SNPs). Under the best-fitting recessive model, homozygous status (GG) at the most strongly associated SNP (rs8069176) conferred an increase in risk by a factor of 2.9, as compared with other genotypes (AG and AA) in the group exposed to environmental tobacco smoke (P=2.8x10(-6); P=0.006 for the test for heterogeneity of the SNP effect on early-onset asthma between groups with tobacco exposure and those without such exposure). CONCLUSIONS: This study shows that the increased risk of asthma conferred by 17q21 genetic variants is restricted to early-onset asthma and that the risk is further increased by early-life exposure to environmental tobacco smoke. These findings provide a greater understanding of the functional role of the 17q21 variants in the pathophysiology of asthma.
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Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
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Self-citationGenetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma
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Outcome of Asthma and Wheezing in the First 6 Years of Life
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Aiolos Regulates B Cell Activation and Maturation to Effector State
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Cited by
A large-scale, consortium-based genomewide association study of asthma
Moffatt, M. F., Gut, I. G., Demenais, F., Strachan, D. P., Bouzigon, E., Heath, S., von Mutius, E., Farrall, M., Lathrop, M., & Cookson, W. O. C. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0906312 · Cited by 1,818
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Genomewide Association Studies and Human Disease
Hardy, J., & Singleton, A. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0808700 · Cited by 733
The genetics of asthma and allergic disease: a 21st century perspective
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Metadata
- Authors
- Bouzigon, E., Corda, E., Aschard, H., Dizier, M.-H., Boland, A., Bousquet, J., Chateigner, N., Gormand, F., Just, J., Le Moual, N., Scheinmann, P., Siroux, V., Vervloet, D., Zelenika, D., Pin, I., Kauffmann, F., Lathrop, M., & Demenais, F.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-11-06
- Volume
- 359
- Issue
- 19
- Pages
- 1985-1994
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2072063345
- Cited by
- 400
- References
- 37
- FWCI
- 21.92
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Bouzigon, E., Corda, E., Aschard, H., Dizier, M.-H., Boland, A., Bousquet, J., Chateigner, N., Gormand, F., Just, J., Le Moual, N., Scheinmann, P., Siroux, V., Vervloet, D., Zelenika, D., Pin, I., Kauffmann, F., Lathrop, M., & Demenais, F. (2008). Effect of 17q21 Variants and Smoking Exposure in Early-Onset Asthma. New England Journal of Medicine. https://doi.org/10.1056/nejmoa0806604
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