دورية أكاديمية
Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD
| العنوان: | Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD |
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| المؤلفون: | Sun, Wei, Kechris, Katerina, Jacobson, Sean, Drummond, M. Bradley, Hawkins, Gregory A., Yang, Jenny, Chen, Ting-huei, Quibrera, Pedro Miguel, Anderson, Wayne, Barr, R. Graham, Basta, Patricia V., Bleecker, Eugene R., Beaty, Terri, Casaburi, Richard, Castaldi, Peter, Cho, Michael H., Comellas, Alejandro, Crapo, James D., Criner, Gerard, Demeo, Dawn, Christenson, Stephanie A., Couper, David J., Curtis, Jeffrey L., Doerschuk, Claire M., Freeman, Christine M., Gouskova, Natalia A., Han, MeiLan K., Hanania, Nicola A., Hansel, Nadia N., Hersh, Craig P., Hoffman, Eric A., Kaner, Robert J., Kanner, Richard E., Kleerup, Eric C., Lutz, Sharon, Martinez, Fernando J., Meyers, Deborah A., Peters, Stephen P., Regan, Elizabeth A., Rennard, Stephen I., Scholand, Mary Beth, Silverman, Edwin K., Woodruff, Prescott G., O’Neal, Wanda K., Bowler, Russell P. |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2016 |
| المجموعة: | Harvard University: DASH - Digital Access to Scholarship at Harvard |
| مصطلحات موضوعية: | Biology and Life Sciences, Biochemistry, Biomarkers, Medicine and Health Sciences, Pulmonology, Chronic Obstructive Pulmonary Disease, Computational Biology, Genome Analysis, Genome-Wide Association Studies, Genetics, Genomics, Human Genetics, Anatomy, Body Fluids, Blood, Physiology, Hematology, Emphysema, Gene Expression, Mathematical and Statistical Techniques, Statistical Methods, Meta-Analysis, Physical Sciences, Mathematics, Statistics (Mathematics), Phenotypes |
| الوصف: | Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1553-7390 |
| العلاقة: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988780/pdfTest/; PLoS Genetics; Sun, W., K. Kechris, S. Jacobson, M. B. Drummond, G. A. Hawkins, J. Yang, T. Chen, et al. 2016. “Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD.” PLoS Genetics 12 (8): e1006011. doi:10.1371/journal.pgen.1006011. http://dx.doi.org/10.1371/journal.pgen.1006011Test.; http://nrs.harvard.edu/urn-3:HUL.InstRepos:29002451Test |
| DOI: | 10.1371/journal.pgen.1006011 |
| الإتاحة: | https://doi.org/10.1371/journal.pgen.1006011Test http://nrs.harvard.edu/urn-3:HUL.InstRepos:29002451Test |
| رقم الانضمام: | edsbas.E7C69843 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15537390 |
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| DOI: | 10.1371/journal.pgen.1006011 |