Genome-Wide Association Study in Patients With Nontuberculous Mycobacterial Lung Disease

Mycobacterium Infections, Nontuberculous Clinical Trial

Official title:

Elucidation of Genetic Susceptibility of Patients With Nontuberculous Mycobacterial Lung Disease Using Genome-Wide Association Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02832843
• Other study ID #: H-1605-111-763
• Status: Completed
• Start date: July 11, 2016
• Est. completion date: October 3, 2019

Study information

• Verified date: December 2019
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this study was to elucidate genetic susceptibility of patients with nontuberculous mycobacterial lung disease using genome-wide association study.

Description:

Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms. NTM lung disease is increasing, however, genetic susceptibility of patients with the disease have not been identified. To elucidate the genetic susceptibility of NTM lung disease, the investigators perform a genome-wide association study (GWAS) including patients with NTM lung disease and healthy controls (case : control = 1 : 3). The age-, sex-matched control group will be recruited from the Korean Healthy Twin Study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2808
• Est. completion date: October 3, 2019
• Est. primary completion date: November 20, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Case: Patients with NTM lung disease satisfying diagnostic criteria suggested by American Thoracic Society

• Control: Healthy subjects enrolled in the Korean Healthy Twin Study

Exclusion Criteria:

• Case: none

• Control: 1) Subjects who have respiratory symptoms including cough and sputum 2) Subjects who have abnormalities on chest radiography

Related Conditions & MeSH terms

• Lung Diseases
• Mycobacterium Infections
• Mycobacterium Infections, Nontuberculous

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (12)

1000 Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA. A map of human genome variation from population-scale sequencing. Nature. 2010 Oct 28;467(7319):1061-73. doi: 10.1038/nature09534. Erratum in: Nature. 2011 May 26;473(7348):544. Xue, Yali [added]; Cartwright, Reed A [added]; Altshuler, David L [corrected to Altshuler, David]; Kebbel, Andrew [corrected to Keebler, Jonathan]; Koko-Gonzales, Paula [corrected to Kokko-Gonzales, Paula]; Nickerson, Debbie A [corrected to Nickerson, Debo. — View Citation

Hill AV. Evolution, revolution and heresy in the genetics of infectious disease susceptibility. Philos Trans R Soc Lond B Biol Sci. 2012 Mar 19;367(1590):840-9. doi: 10.1098/rstb.2011.0275. Review. — View Citation

Howie BN, Donnelly P, Marchini J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 2009 Jun;5(6):e1000529. doi: 10.1371/journal.pgen.1000529. Epub 2009 Jun 19. — View Citation

Kim J, Seong MW, Kim EC, Han SK, Yim JJ. Frequency and clinical implications of the isolation of rare nontuberculous mycobacteria. BMC Infect Dis. 2015 Jan 9;15:9. doi: 10.1186/s12879-014-0741-7. — View Citation

Kim RD, Greenberg DE, Ehrmantraut ME, Guide SV, Ding L, Shea Y, Brown MR, Chernick M, Steagall WK, Glasgow CG, Lin J, Jolley C, Sorbara L, Raffeld M, Hill S, Avila N, Sachdev V, Barnhart LA, Anderson VL, Claypool R, Hilligoss DM, Garofalo M, Fitzgerald A, Anaya-O'Brien S, Darnell D, DeCastro R, Menning HM, Ricklefs SM, Porcella SF, Olivier KN, Moss J, Holland SM. Pulmonary nontuberculous mycobacterial disease: prospective study of a distinct preexisting syndrome. Am J Respir Crit Care Med. 2008 Nov 15;178(10):1066-74. doi: 10.1164/rccm.200805-686OC. Epub 2008 Aug 14. — View Citation

Kwak N, Lee CH, Lee HJ, Kang YA, Lee JH, Han SK, Yim JJ. Non-tuberculous mycobacterial lung disease: diagnosis based on computed tomography of the chest. Eur Radiol. 2016 Dec;26(12):4449-4456. Epub 2016 Mar 5. — View Citation

Lee AR, Lee J, Choi SM, Seong MW, Kim SA, Kim M, Chae KO, Lee JS, Yim JJ. Phenotypic, immunologic, and clinical characteristics of patients with nontuberculous mycobacterial lung disease in Korea. BMC Infect Dis. 2013 Nov 25;13:558. doi: 10.1186/1471-2334-13-558. — View Citation

Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol. 2010 Dec;34(8):816-34. doi: 10.1002/gepi.20533. — View Citation

Park YS, Lee CH, Lee SM, Yang SC, Yoo CG, Kim YW, Han SK, Shim YS, Yim JJ. Rapid increase of non-tuberculous mycobacterial lung diseases at a tertiary referral hospital in South Korea. Int J Tuberc Lung Dis. 2010 Aug;14(8):1069-71. — View Citation

Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, Moore JH. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet. 2001 Jul;69(1):138-47. Epub 2001 Jun 11. — View Citation

Sung J, Cho SI, Lee K, Ha M, Choi EY, Choi JS, Kim H, Kim J, Hong KS, Kim Y, Yoo KY, Park C, Song YM. Healthy Twin: a twin-family study of Korea--protocols and current status. Twin Res Hum Genet. 2006 Dec;9(6):844-8. — View Citation

Yim JJ, Kim HJ, Kwon OJ, Koh WJ. Association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and nontuberculous mycobacterial lung disease in a Korean population. Hum Immunol. 2008 Sep;69(9):572-6. doi: 10.1016/j.humimm.2008.06.003. Epub 2008 Jul 3. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Finding of single nucleotide polymorphisms (SNPs) associated with the risk of NTM lung disease compared with controls	To identify SNPs related to NTM lung disease using logistic regression after controlling for confounders (GWAS statistical significance threshold, P < 5.00*E-08)	Baseline
Secondary	Finding of SNPs associated with the risk of severe NTM lung disease compared with controls	To identify SNPs related to severe NTM lung disease compared with controls using logistic regression after controlling for confounders (GWAS statistical significance threshold, P < 5.00*E-08)	Baseline
Secondary	Finding of SNPs associated with the risk of severe NTM lung disease compared with mild NTM lung disease	To identify SNPs related to severe NTM lung disease compared with mild NTM lung disease using logistic regression after controlling for confounders (GWAS statistical significance threshold, P < 5.00*E-08)	Baseline
Secondary	Finding of SNPs associated with the risk of Mycobacterium avium complex lung disease versus M. abscessus lung disease versus controls	To identify SNPs related to Mycobacterium avium complex lung disease versus M. abscessus lung disease versus controls using multinomial logistic regression after controlling for confounders (GWAS statistical significance threshold, P < 5.00*E-08)	Baseline