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Risk prediction of pulmonary tuberculosis using genetic and conventional risk factors in adult Korean population

Title
Risk prediction of pulmonary tuberculosis using genetic and conventional risk factors in adult Korean population
Authors
Hong, Eun PyoGo, Min JinKim, Hyung-LaePark, Ji Wan
Ewha Authors
김형래
SCOPUS Author ID
김형래scopus
Issue Date
2017
Journal Title
PLOS ONE
ISSN
1932-6203JCR Link
Citation
vol. 12, no. 3
Publisher
PUBLIC LIBRARY SCIENCE
Indexed
SCIE; SCOPUS WOS
Abstract
A complex interplay among host, pathogen, and environmental factors is believed to contribute to the risk of developing pulmonary tuberculosis (PTB). The lack of replication of published genome-wide association study (GWAS) findings limits the clinical utility of reported single nucleotide polymorphisms (SNPs). We conducted a GWAS using 467 PTB cases and 1,313 healthy controls obtained from two community -based cohorts in Korea. We evaluated the performance of PTB risk models based on different combinations of genetic and nongenetic factors and validated the results in an independent Korean population comprised of 179 PTB cases and 500 healthy controls. We demonstrated the polygenic nature of PTB and nongenetic factors such as age, sex, and body mass index (BMI) were strongly associated with PTB risk. None of the SNPs achieved genome-wide significance; instead, we were able to replicate the associations between PTB and ten SNPs near or in the genes, CDCA7, GBE1, GADL1, SPATA16, C6orf118, KIAA1432, DMRT2, CTR9, CCDC67, and CDH13, which may play roles in the immune and inflammatory pathways. Among the replicated SNPs, an intergenic SNP, rs9365798, located downstream of the C6orf118 gene showed the most significant association under the dominant model (OR = 1.59, 95% CI 1.32-1.92, P= 2.1x10-6). The performance of a risk model combining the effects of ten replicated SNPs and six nongenetic factors (i.e., age, sex, BMI, cigarette smoking, systolic blood pressure, and hemoglobin) were validated in the replication set (AUC = 0.80, 95% CI 0.76-0.84). The strategy of combining genetic and nongenetic risk factors ultimately resulted in better risk prediction for PTB in the adult Korean population.
DOI
10.1371/journal.pone.0174642
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의과대학 > 의학과 > Journal papers
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