[HTML][HTML] Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis

H Corvol, SM Blackman, PY Boëlle, PJ Gallins… - Nature …, 2015 - nature.com
H Corvol, SM Blackman, PY Boëlle, PJ Gallins, RG Pace, JR Stonebraker, FJ Accurso
Nature communications, 2015nature.com
The identification of small molecules that target specific CFTR variants has ushered in a new
era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require
identification and targeting of disease modifiers. Here we use genome-wide association
analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-
analysis of 6,365 CF patients identifies five loci that display significant association with
variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P= 3.3× 10− 11), chr5p15. 3 …
Abstract
The identification of small molecules that target specific CFTR variants has ushered in a new era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require identification and targeting of disease modifiers. Here we use genome-wide association analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-analysis of 6,365 CF patients identifies five loci that display significant association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3 × 10−11), chr5p15.3 (SLC9A3; P=6.8 × 10−12), chr6p21.3 (HLA Class II; P=1.2 × 10−8) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 × 10−9) contain genes of high biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13 (EHF/APIP; P=1.9 × 10−10), was previously shown to be associated with lung disease. These results provide new insights into potential targets for modulating lung disease severity in CF.
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