Genotype-Phenotype Models Predicting (V)over dotO_2max Response to High-Intensity Interval Training in Physically Inactive Chinese

Purpose: This study aimed to analyze the interindividual differences of the maximal oxygen uptake ((V)over dotO(2max)) response to 12wk of high-intensity interval training (HIIT), and the genotype-phenotype models were constructed to predict the effect of HIIT on (V)over dotO(2max). Methods: A total of 228 physically inactive adults who completed a 12-wk HIIT were analyzed. A genome-wide association study (GWAS) was conducted to identify genetic variants associated with the (V)over dotO(2max) response. Nonresponders, responders, and the highest training responders were defined as the effect sizes (ES) <0.2, >= 0.2, and >= 0.8, respectively. We generated polygenic predictor score (PPS) using lead variants and constructed a predictive model for (V)over dotO(2max) response based on a linear stepwise regression analysis. Results: The (V)over dotO(2max) increased significantly after HIIT (similar to 14%, P < 0.001), but with interindividual differences (-7.8 to 17.9 mL.kg(-1).min(-1)). In 27% of participants, the (V)over dotO(2max) showed no improvement. We identified one genetic locus near the gamma-aminobutyric acid type A receptor subunit beta 3 gene (GABRB3, rs17116985) associated with (V)over dotO(2max) response at the genome-wide significance level (P < 5 x 10(-8)), and an additional nine single nucleotide polymorphisms (SNPs) at the suggestive significance level (P < 1 x 10(-5)). The SNPs rs474377, rs9365605, and rs17116985, respectively, explained 11%, 9%, and 6.2% of variance in (V)over dotO(2max) response. The 13 SNPs (P < 1 x 10(-5)) were found on chromosome 6 (position: 148209316-148223568). Individuals with a PPS greater than 1.757 had the highest response, and those with a PPS lower than -3.712 were nonresponders. The PPS, baseline (V)over dotO(2max), sex, and body mass explained 56.4% of the variance in the (V)over dotO(2max) response; the major predictor was the PPS, which explained 39.4% of the variance. Conclusions: The PPS, baseline (V)over dotO(2max), sex, and body mass could explain the variance in (V)over dotO(2max) response. Individuals who had a PPS greater than 1.757 had the highest training response after 12 wk of HIIT. Genetic variants in a region on chromosome 6, especially the sterile alpha motif domain containing 5 gene (SAMD5), which had been explored influencing angiogenesis, might have a potential role in the (V)over dotO(2max) response.