Exome Array Analysis Identifies a Common Variant in IL27 Associated with Chronic Obstructive Pulmonary Disease.
PBN-AR
Instytucja
Instytut Gruźlicy i Chorób Płuc
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
Am J Respir Crit Care Med
ISSN
1073-449X
EISSN
1535-4970
Wydawca
New York, NY : American Lung Association,
DOI
Rok publikacji
2016
Numer zeszytu
1
Strony od-do
48-57
Numer tomu
194
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Autorzy
(liczba autorów: 24)
Pozostali autorzy
+ 23
Autorzy przekładu
(liczba autorów przekładu: 0)
Słowa kluczowe
angielski
IL-27; chronic obstructive pulmonary disease; exome; genetics
Streszczenia
Język
angielski
Treść
RATIONALE: Chronic obstructive pulmonary disease (COPD) susceptibility is in part related to genetic variants. Most genetic studies have been focused on genome-wide common variants without a specific focus on coding variants, but common and rare coding variants may also affect COPD susceptibility. OBJECTIVES: To identify coding variants associated with COPD. METHODS: We tested nonsynonymous, splice, and stop variants derived from the Illumina HumanExome array for association with COPD in five study populations enriched for COPD. We evaluated single variants with a minor allele frequency greater than 0.5% using logistic regression. Results were combined using a fixed effects meta-analysis. We replicated novel single-variant associations in three additional COPD cohorts. MEASUREMENTS AND MAIN RESULTS: We included 6,004 control subjects and 6,161 COPD cases across five cohorts for analysis. Our top result was rs16969968 (P = 1.7 × 10(-14)) in CHRNA5, a locus previously associated with COPD susceptibility and nicotine dependence. Additional top results were found in AGER, MMP3, and SERPINA1. A nonsynonymous variant, rs181206, in IL27 (P = 4.7 × 10(-6)) was just below the level of exome-wide significance but attained exome-wide significance (P = 5.7 × 10(-8)) when combined with results from other cohorts. Gene expression datasets revealed an association of rs181206 and the surrounding locus with expression of multiple genes; several were differentially expressed in COPD lung tissue, including TUFM. CONCLUSIONS: In an exome array analysis of COPD, we identified nonsynonymous variants at previously described loci and a novel exome-wide significant variant in IL27. This variant is at a locus previously described in genome-wide associations with diabetes, inflammatory bowel disease, and obesity and appears to affect genes potentially related to COPD pathogenesis.
Inne
System-identifier
PX-5894712182ce4a248cecdcc1
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