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

TitleGenome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2.
Publication TypeJournal Article
Year of Publication2011
AuthorsWright, FA, Strug, LJ, Doshi, VK, Commander, CW, Blackman, SM, Sun, L, Berthiaume, Y, Cutler, D, Cojocaru, A, J Collaco, M, Corey, M, Dorfman, R, Goddard, K, Green, D, Kent, JW, Lange, EM, Lee, S, Li, W, Luo, J, Mayhew, GM, Naughton, KM, Pace, RG, Paré, P, Rommens, JM, Sandford, A, Stonebraker, JR, Sun, W, Taylor, C, Vanscoy, LL, Zou, F, Blangero, J, Zielenski, J, O'Neal, WK, Drumm, ML, Durie, PR, Knowles, MR, Cutting, GR
JournalNat Genet
Volume43
Issue6
Pagination539-46
Date Published2011 Jun
ISSN1546-1718
KeywordsAdolescent, Adult, Child, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 20, Cystic Fibrosis, Female, Genetic Linkage, Genome-Wide Association Study, Humans, Lung Diseases, Male, Phenotype, Quantitative Trait Loci
Abstract

A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10(-8)) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del 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 quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder.

DOI10.1038/ng.838
Alternate JournalNat. Genet.
PubMed ID21602797
PubMed Central IDPMC3296486
Grant ListHG-0004314 / HG / NHGRI NIH HHS / United States
K23 DK083551 / DK / NIDDK NIH HHS / United States
K23DK083551 / DK / NIDDK NIH HHS / United States
MH059490 / MH / NIMH NIH HHS / United States
P30 DK027651 / DK / NIDDK NIH HHS / United States
P30DK027651 / DK / NIDDK NIH HHS / United States
R01 HL068890 / HL / NHLBI NIH HHS / United States
R01 HL068927 / HL / NHLBI NIH HHS / United States
R01 HL068927-10 / HL / NHLBI NIH HHS / United States
R01DK066368 / DK / NIDDK NIH HHS / United States
R01HL068890 / HL / NHLBI NIH HHS / United States
R01HL068927 / HL / NHLBI NIH HHS / United States
R01HL095396 / HL / NHLBI NIH HHS / United States
T32 HL072748 / HL / NHLBI NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada