Genome-wide association study for genetic variants related with maximal voluntary ventilation reveals two novel genomic signals associated with lung function

Genome-wide association studies (GWAS) for spirometry parameters have been limited to forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), and their ratio. This study examined to identify genetic variants associated with maximal voluntary ventilation (MVV), an important spirometry parameter presenting inspiratory muscle strength. A total of 8842 Korean subjects participated in the Korean Association REsource Consortium were used to identify nucleotide variants associated with MVV and other spirometry parameters through a GWAS. Genetic associations were determined by employing a mixed model that can control background polygenic effects. The analysis revealed 3 nucleotide variants associated with MVV (P < 5 × 10(−8)). One (rs1496255) was also associated with FVC and FEV(1). The other 2 variants were identified only for MVV and located in the genes of LOC102724340 (rs41434646) and FHIT (rs9833533). In particular, FHIT represses transcriptional activity of β-catenin, a critical protein for growth of skeletal muscle, and thus might have influenced the level of MVV. The current study revealed 2 novel nucleotide variants as genetic association signals for MVV. The association signals were suggested specific for neuromuscular diseases with a restrictive ventilatory impairment. Further studies are required to understand underlying mechanisms for their influence to restrictive lung diseases.