Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10(-8)) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (...

Descripción completa

Detalles Bibliográficos
Autores principales: Wright, Fred A., Strug, Lisa J., Doshi, Vishal K., Commander, Clayton W., Blackman, Scott M., Sun, Lei, Berthiaume, Yves, Cutler, David, Cojocaru, Andreea, Collaco, J. Michael, Corey, Mary, Dorfman, Ruslan, Goddard, Katrina, Green, Deanna, Kent, Jack W., Lange, Ethan M., Lee, Seunggeun, Li, Weili, Luo, Jingchun, Mayhew, Gregory M., Naughton, Kathleen M., Pace, Rhonda G., Paré, Peter, Rommens, Johanna M., Sandford, Andrew, Stonebraker, Jaclyn R., Sun, Wei, Taylor, Chelsea, Vanscoy, Lori L., Zou, Fei, Blangero, John, Zielenski, Julian, O’Neal, Wanda K., Drumm, Mitchell L., Durie, Peter R., Knowles, Michael R., Cutting, Garry R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296486/
https://www.ncbi.nlm.nih.gov/pubmed/21602797
http://dx.doi.org/10.1038/ng.838
Descripción
Sumario:A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10(-8)) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10(-9) for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder.

Ejemplares similares