作者@article {Namkoong1902269 = {Namkoong,何鸿燊and Omae, Yosuke and Asakura, Takanori and Ishii, Makoto and Suzuki, Shoji and Morimoto, Kozo and Kawai, Yosuke and Emoto, Katsura and Oler, Andrew J. and Szymanski, Eva P. and Yoshida, Mitsunori and Matsuda, Shuichi and Yagi, Kazuma and Hase, Isano and Nishimura, Tomoyasu and Sasaki, Yuka and Asami, Takahiro and Shiomi, Tetsuya and Matsubara, Hiroaki and Shimada, Hisato and Hamamoto, Junko and Jhun, Byung Woo and Kim, Su-Young and Huh, Hee Jae and Won, Hong-Hee and Ato, Manabu and Kosaki, Kenjiro and Betsuyaku, Tomoko and Fukunaga, Koichi and Kurashima, Atsuyuki and Tettelin, Herv{\'e} and Yanai, Hideki and Mahasirimongkol, Surakameth and Olivier, Kenneth N. and Hoshino, Yoshihiko and Koh, Won-Jung and Holland, Steven M. and Tokunaga, Katsushi and Hasegawa, Naoki and the Nontuberculous Mycobacteriosis and Bronchiectasis {\textendash} Japan Research Consortium (NTM-JRC)}, title = {Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease}, volume = {58}, number = {2}, elocation-id = {1902269}, year = {2021}, doi = {10.1183/13993003.02269-2019}, publisher = {European Respiratory Society}, abstract = {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{\texttimes}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{\texttimes}10-12, OR 0.54) and European (p=5.12{\texttimes}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}, issn = {0903-1936}, URL = {//www.qdcxjkg.com/content/58/2/1902269}, eprint = {//www.qdcxjkg.com/content/58/2/1902269.full.pdf}, journal = {European Respiratory Journal} }