한빛사 논문
Jaeyoung Cho1, Kyungtaek Park2, Sun Mi Choi1, Jinwoo Lee1,3, Chang-Hoon Lee1, Jung-Kyu Lee4, Eun Young Heo4, Deog Kyeom Kim3,4, Yeon Joo Lee5, Jong Sun Park3,5, Young-Jae Cho5, Ho Il Yoon3,5, Jae Ho Lee3,5, Choon-Taek Lee3,5, Nayoung Kim3,6, Kyu Yeong Choi7, Kun Ho Lee7,8,9, Joohon Sung10,11, Sungho Won2,10,11, Jae-Joon Yim1,3
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
2Interdisciplinary Program of Bioinformatics, Seoul National University College of Natural Sciences, Seoul, Korea (the Republic of)
3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
4Division of Pulmonary and Critical Care Medicine, Seoul Metropolitan Government–Seoul National University Boramae Medical Center, Dongjak-gu, Seoul, Korea (the Republic of)
5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea (the Republic of)
6Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea (the Republic of)
7Gwangju Alzheimer’s disease and Related Dementia Cohort Research Center, Chosun University, Gwangju, Korea (the Republic of)
8Department of Biomedical Science, Chosun University, Gwangju, Korea (the Republic of)
9Aging Neuroscience Research Group, Korea Brain Research Institute, Daegu, Korea (the Republic of)
10Department of Public Health Sciences, Seoul National University Graduate School of Public Health, Seoul, Korea (the Republic of)
11Seoul National University Institute of Health and Environment, Seoul, Korea (the Republic of)
JC and KP contributed equally.
Correspondence to Dr Jae-Joon Yim, Professor Sungho Won
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.
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기