Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease
Title: Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease
Authors: Ho Namkoong, Yosuke Omae, Takanori Asakura, Makoto Ishii, Shoji Suzuki, Kozo Morimoto, Yosuke Kawai, Katsura Emoto, Andrew J. Oler, Eva P. Szymanski, Mitsunori Yoshida, Shuichi Matsuda, Kazuma Yagi, Isano Hase, Tomoyasu Nishimura, Yuka Sasaki, Takahiro Asami, Tetsuya Shiomi, Hiroaki Matsubara, Hisato Shimada, Junko Hamamoto, Byung Woo Jhun, Su-Young Kim, Hee Jae Huh, Hong-Hee Won, Manabu Ato, Kenjiro Kosaki, Tomoko Betsuyaku, Koichi Fukunaga, Atsuyuki Kurashima, Hervé Tettelin, Hideki Yanai, Surakameth Mahasirimongkol, Kenneth N. Olivier, Yoshihiko Hoshino, Won-Jung Koh, Steven M. Holland, Katsushi Tokunaga, Naoki Hasegawa
Journal: European Respiratory Journal, Vol 58, Issue 2 (2021)
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.
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