title: Role of Lung Function Genes in the Development of Asthma.
abstract: Although our previous GWAS failed to identify SNPs associated with pulmonary function at the level of genomewide significance, it did show that the heritability for FEV1/FVC was 41.6% in a Japanese population, suggesting that the heritability of pulmonary function traits can be explained by the additive effects of multiple common SNPs. In addition, our previous study indicated that pulmonary function genes identified in previous GWASs in non-Japanese populations accounted for 4.3% to 12.0% of the entire estimated heritability of FEV1/FVC in a Japanese population. Therefore, given that many loci with individual weak effects may contribute to asthma risk, in this study, we created a quantitative score of genetic load based on 16 SNPs implicated in lower lung function in both Japanese and non-Japanese populations. This genetic risk score (GRS) for lower FEV1/FVC was consistently associated with the onset of asthma (P = 9.6 × 10(-4)) in 2 independent Japanese populations as well as with the onset of COPD (P = 0.042). Clustering of asthma patients based on GRS levels indicated that an increased GRS may be responsible for the development of a particular phenotype of asthma characterized by early onset, atopy, and severer airflow obstruction.
authors.affiliation: Department of Pulmonology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Pulmonology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Masuko
authors.affiliation: Department of Pulmonology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yatagai
authors.affiliation: Department of Pulmonology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Pulmonology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Tsukuba Medical Center, Tsukuba, Ibaraki, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iijima
authors.affiliation: Tsukuba Medical Center, Tsukuba, Ibaraki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Naito
authors.affiliation: Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Noguchi
authors.affiliation: Laboratory for Respiratory Diseases, Center for Genomic Medicine, Institute of Physical and Chemical Research, Tsurumi, Kanagawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Konno
authors.affiliation: Laboratory for Respiratory Diseases, Center for Genomic Medicine, Institute of Physical and Chemical Research, Tsurumi, Kanagawa, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hirota
authors.affiliation: First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
authors.affiliation: Department of Pulmonology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hizawa
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001249:Asthma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D019655:Quantitative Trait, Heritable; D012306:Risk; D014797:Vital Capacity / Q000235:genetics*