Abstract
BACKGROUND: Previous genome-wide association studies (GWAS) have established association between genetic variants and pulmonary function across various ethnics, whereas such associations are scarcely reported in Chinese adults. Therefore, we conducted an GWAS to explore relationships between genetic variants and pulmonary function among middle-aged Chinese dizygotic twins and further validated the top variants using data from the UK Biobank (UKB). METHODS: In the discovery phase, 139 dizygotic twin pairs were drawn from the Qingdao Twin Registry. Pulmonary function was assessed using three parameters: forced expiratory volume the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. GWAS was performed using GEMMA, Gene-based analysis was conducted by VEGAS2. And pathway enrichment analysis was performed using PASCAL. In the validation phase, Single-nucleotide polymorphisms (SNPs) with suggestive significance were examined through linear regression analysis of the additive effect model among 1573 Chinese ethnic participants from UKB. RESULTS: The median age of twin pairs in the study was 49 years. 3 SNPs (rs80345886, rs117883876, and 75139439) related to FEV1 achieved genome-wide significance. Moreover, 222, 150, and 73 SNPs surpassed suggestive evidence level (p < 1 × 10(- 5)) for FEV1, FVC, and FEV1/FVC, respectively. Among them, 16 SNPs located in TBC1D16 for FEV1, 25 SNPs located in GPR126 for FVC, and 2 SNPs located in CCDC110 for FEV1/FVC, the three genes were also revealed by gene-based analysis. Moreover, 12 novel SNPs related to pulmonary function were validated to reach the nominal significance level (p < 0.05) in the UKB, with some located in the TBC1D16, TAFA5, and MTHFD1L genes. CONCLUSION: Our GWAS results on Chinese dizygotic twins provide new references for the genetic regulation on pulmonary function. Twelve novel susceptibility loci are considered as possible crucial to pulmonary function.