title: Risk prediction of pulmonary tuberculosis using genetic and conventional risk factors in adult Korean population.
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 = 2.1×10-6). 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.
authors.affiliation: Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon-si, Ganwon-do, Republic of Korea.
authors.forename: Eun Pyo
authors.initials: EP
authors.lastname: Hong
authors.affiliation: Center for Genome Science, National Institute of Health, Cheongju-si, Chungcheongbuk-do, Republic of Korea.
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Go
authors.affiliation: Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Hyung-Lae
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon-si, Ganwon-do, Republic of Korea.
authors.forename: Ji Wan
authors.identifier: http://orcid.org/0000-0003-0840-1696
authors.initials: JW
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006004:Glycogen Debranching Enzyme System / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D012907:Smoking; D014397:Tuberculosis, Pulmonary / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology
chemical_list: C445325:CDCA7 protein, human; D006004:Glycogen Debranching Enzyme System; D009687:Nuclear Proteins; C577876:GBE1 protein, human