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Original research
Genome-wide association study of non-tuberculous mycobacterial pulmonary disease
  1. Jaeyoung Cho1,
  2. Kyungtaek Park2,
  3. Sun Mi Choi1,
  4. Jinwoo Lee1,3,
  5. Chang-Hoon Lee1,
  6. Jung-Kyu Lee4,
  7. Eun Young Heo4,
  8. Deog Kyeom Kim3,4,
  9. Yeon Joo Lee5,
  10. Jong Sun Park3,5,
  11. Young-Jae Cho5,
  12. Ho Il Yoon3,5,
  13. Jae Ho Lee3,5,
  14. Choon-Taek Lee3,5,
  15. Nayoung Kim3,6,
  16. Kyu Yeong Choi7,
  17. Kun Ho Lee7,8,9,
  18. Joohon Sung10,11,
  19. Sungho Won2,10,11,
  20. Jae-Joon Yim1,3
  1. 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  2. 2Interdisciplinary Program of Bioinformatics, Seoul National University College of Natural Sciences, Seoul, Korea (the Republic of)
  3. 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  4. 4Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government–Seoul National University Boramae Medical Center, Dongjak-gu, Seoul, Korea (the Republic of)
  5. 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea (the Republic of)
  6. 6Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea (the Republic of)
  7. 7Gwangju Alzheimer’s disease and Related Dementia Cohort Research Center, Chosun University, Gwangju, Korea (the Republic of)
  8. 8Department of Biomedical Science, Chosun University, Gwangju, Korea (the Republic of)
  9. 9Aging Neuroscience Research Group, Korea Brain Research Institute, Daegu, Korea (the Republic of)
  10. 10Department of Public Health Sciences, Seoul National University Graduate School of Public Health, Seoul, Korea (the Republic of)
  11. 11Seoul National University Institute of Health and Environment, Seoul, Korea (the Republic of)
  1. Correspondence to Dr Jae-Joon Yim, Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea (the Republic of); yimjj{at}snu.ac.kr; Professor Sungho Won, Department of Public Health Sciences, Seoul National University Graduate School of Public Health, Seoul, Korea (the Republic of); won1{at}snu.ac.kr

Abstract

Background The prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in South Korea and many parts of the world. However, the genetic factors underlying susceptibility to this disease remain elusive.

Methods To identify genetic variants in patients with NTM-PD, we performed a genome-wide association study with 403 Korean patients with NTM-PD and 306 healthy controls from the Healthy Twin Study, Korea cohort. Candidate variants from the discovery cohort were subsequently validated in an independent cohort. The Genotype-Tissue Expression (GTEx) database was used to identify expression quantitative trait loci (eQTL) and to conduct Mendelian randomisation (MR).

Results We identified a putatively significant locus on chromosome 7p13, rs849177 (OR, 2.34; 95% CI, 1.71 to 3.21; p=1.36×10−7), as the candidate genetic variant associated with NTM-PD susceptibility. Its association was subsequently replicated and the combined p value was 4.92×10−8. The eQTL analysis showed that a risk allele at rs849177 was associated with lower expression levels of STK17A, a proapoptotic gene. In the MR analysis, a causal effect of STK17A on NTM-PD development was identified (β, −4.627; 95% CI, −8.768 to −0.486; p=0.029).

Conclusions The 7p13 genetic variant might be associated with susceptibility to NTM-PD in the Korean population by altering the expression level of STK17A.

  • atypical mycobacterial infection
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Footnotes

  • JC and KP contributed equally.

  • Contributors JJY and SW had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. JC, KP, JJY and SW contributed to the study concept and design, analysis and interpretation of data, and writing and revision of the manuscript. SMC, JL, CHL, JKL, EYH, DKK, YJL, JSP, YJC, HIY, JHL, CTL, NK, KYC, KHL and JS contributed to patient enrolment and data acquisition. All authors read and approved the final manuscript.

  • Funding This work was supported by the Seoul National University College of Medicine Research Fund (Grant number 0320160080).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by Institutional Review Board of Seoul National University Hospital (H-1605-111-763), Seoul National University Bundang Hospital (B-1610/366–303) and Chosun University (CHOSUN 2013-12-018-066).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Contact details: Jae-Joon Yim, MD, yimjj@snu.ac.kr.

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