TY - JOUR
T1 - Genetic loci for lung function in Japanese adults with adjustment for exhaled nitric oxide levels as airway inflammation indicator
AU - Yamada, Mitsuhiro
AU - Motoike, Ikuko N.
AU - Kojima, Kaname
AU - Fuse, Nobuo
AU - Hozawa, Atsushi
AU - Kuriyama, Shinichi
AU - Katsuoka, Fumiki
AU - Tadaka, Shu
AU - Shirota, Matsuyuki
AU - Sakurai, Miyuki
AU - Nakamura, Tomohiro
AU - Hamanaka, Yohei
AU - Suzuki, Kichiya
AU - Sugawara, Junichi
AU - Ogishima, Soichi
AU - Uruno, Akira
AU - Kodama, Eiichi N.
AU - Fujino, Naoya
AU - Numakura, Tadahisa
AU - Ichikawa, Tomohiro
AU - Mitsune, Ayumi
AU - Ohe, Takashi
AU - Kinoshita, Kengo
AU - Ichinose, Masakazu
AU - Sugiura, Hisatoshi
AU - Yamamoto, Masayuki
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Lung function reflects the ability of the respiratory system and is utilized for the assessment of respiratory diseases. Because type 2 airway inflammation influences lung function, genome wide association studies (GWAS) for lung function would be improved by adjustment with an indicator of the inflammation. Here, we performed a GWAS for lung function with adjustment for exhaled nitric oxide (FeNO) levels in two independent Japanese populations. Our GWAS with genotype imputations revealed that the RNF5/AGER locus including AGER rs2070600 SNP, which introduces a G82S substitution of AGER, was the most significantly associated with FEV1/FVC. Three other rare missense variants of AGER were further identified. We also found genetic loci with three candidate genes (NOS2, SPSB2 and RIPOR2) associated with FeNO levels. Analyses with the BioBank-Japan GWAS resource revealed genetic links of FeNO and asthma-related traits, and existence of common genetic background for allergic diseases and their biomarkers. Our study identified the genetic locus most strongly associated with airway obstruction in the Japanese population and three genetic loci associated with FeNO, an indicator of type 2 airway inflammation in adults.
AB - Lung function reflects the ability of the respiratory system and is utilized for the assessment of respiratory diseases. Because type 2 airway inflammation influences lung function, genome wide association studies (GWAS) for lung function would be improved by adjustment with an indicator of the inflammation. Here, we performed a GWAS for lung function with adjustment for exhaled nitric oxide (FeNO) levels in two independent Japanese populations. Our GWAS with genotype imputations revealed that the RNF5/AGER locus including AGER rs2070600 SNP, which introduces a G82S substitution of AGER, was the most significantly associated with FEV1/FVC. Three other rare missense variants of AGER were further identified. We also found genetic loci with three candidate genes (NOS2, SPSB2 and RIPOR2) associated with FeNO levels. Analyses with the BioBank-Japan GWAS resource revealed genetic links of FeNO and asthma-related traits, and existence of common genetic background for allergic diseases and their biomarkers. Our study identified the genetic locus most strongly associated with airway obstruction in the Japanese population and three genetic loci associated with FeNO, an indicator of type 2 airway inflammation in adults.
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U2 - 10.1038/s42003-021-02813-8
DO - 10.1038/s42003-021-02813-8
M3 - Article
C2 - 34782693
AN - SCOPUS:85119083658
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 1288
ER -