Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis.
Harriet CorvolScott M BlackmanPierre-Yves BoëllePaul J GallinsRhonda G PaceJaclyn R StonebrakerFrank J AccursoAnnick ClementJoseph M CollacoHong DangAnthony T DangArianna FrancaJiafen GongLoic GuillotKatherine KeenanWeili LiFan LinMichael V PatroneKaren S RaraighLei SunYi-Hui ZhouWanda K O'NealMarci K SontagHara LevyPeter R DurieJohanna M RommensMitchell L DrummFred A WrightLisa J StrugGarry R CuttingMichael R KnowlesPublished in: Nature communications (2015)
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.
Keyphrases
- cystic fibrosis
- genome wide association
- genome wide
- pseudomonas aeruginosa
- lung function
- systematic review
- dna methylation
- copy number
- ejection fraction
- bioinformatics analysis
- randomized controlled trial
- risk assessment
- type diabetes
- risk factors
- drug delivery
- gene expression
- combination therapy
- cardiovascular disease
- meta analyses
- human health