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

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Genome-wide association studies (GWAS) for spirometry parameters have been limited to forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), 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 FEV1. 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.

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