التفاصيل البيبلوغرافية
| العنوان: |
Exome Array Analysis Identifies a Common Variant in IL27 Associated with Chronic Obstructive Pulmonary Disease. |
| المؤلفون: |
Hobbs, Brian D., Parker, Margaret M., Han Chen, Taotao Lao, Hardin, Megan, Dandi Qiao, Hawrylkiewicz, Iwona, Sliwinski, Pawel, Jae-Joon Yim, Woo Jin Kim, Deog Kyeom Kim, Castaldi, Peter J., Hersh, Craig P., Morrow, Jarrett, Celli, Bartolome R., Pinto-Plata, Victor M., Criner, Gerald J., Marchetti, Nathaniel, Bueno, Raphael, Agustí, Alvar |
| المصدر: |
American Journal of Respiratory & Critical Care Medicine; 7/1/2016, Vol. 194 Issue 1, p48-57, 10p, 3 Charts |
| مصطلحات موضوعية: |
DISEASE susceptibility, GENES, GENOMES, INTERLEUKINS, OBSTRUCTIVE lung diseases, RESEARCH funding |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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