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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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, firstname.lastname@example.org.
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