RT期刊文章SR电子T1全基因组sociation study in patients with pulmonaryMycobacterium aviumcomplex disease JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 1902269 DO 10.1183/13993003.02269-2019 VO 58 IS 2 A1 Namkoong, Ho A1 Omae, Yosuke A1 Asakura, Takanori A1 Ishii, Makoto A1 Suzuki, Shoji A1 Morimoto, Kozo A1 Kawai, Yosuke A1 Emoto, Katsura A1 Oler, Andrew J. A1 Szymanski, Eva P. A1 Yoshida, Mitsunori A1 Matsuda, Shuichi A1 Yagi, Kazuma A1 Hase, Isano A1 Nishimura, Tomoyasu A1 Sasaki, Yuka A1 Asami, Takahiro A1 Shiomi, Tetsuya A1 Matsubara, Hiroaki A1 Shimada, Hisato A1 Hamamoto, Junko A1 Jhun, Byung Woo A1 Kim, Su-Young A1 Huh, Hee Jae A1 Won, Hong-Hee A1 Ato, Manabu A1 Kosaki, Kenjiro A1 Betsuyaku, Tomoko A1 Fukunaga, Koichi A1 Kurashima, Atsuyuki A1 Tettelin, Hervé A1 Yanai, Hideki A1 Mahasirimongkol, Surakameth A1 Olivier, Kenneth N. A1 Hoshino, Yoshihiko A1 Koh, Won-Jung A1 Holland, Steven M. A1 Tokunaga, Katsushi A1 Hasegawa, Naoki A1 the Nontuberculous Mycobacteriosis and Bronchiectasis – Japan Research Consortium (NTM-JRC) YR 2021 UL //www.qdcxjkg.com/content/58/2/1902269.abstract AB Rationale Nontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear.Objectives We aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen.Methods This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping.Results The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64×10−13, OR 0.54), which is in an intronic region of the calcineurin-like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. Additionally, this SNP was significantly associated with the disease in patients of Korean (p=2.18×10−12, OR 0.54) and European (p=5.12×10−03, OR 0.63) ancestry.Conclusions We identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease.The first GWAS of pulmonary MAC disease in Japanese, Korean and European patients. SNPs in the CHP2 region were associated with the disease risk. CHP2 may play an important role in host susceptibility to pulmonary MAC disease. https://bit.ly/39iCIio