Genotype-Phenotype Models Predicting V̇O2max Response to High-Intensity Interval Training in Physically Inactive Chinese

ABSTRACT Purpose This study aimed to analyze the interindividual differences of the maximal oxygen uptake (V̇O2max) response to 12 wk of high-intensity interval training (HIIT), and the genotype–phenotype models were constructed to predict the effect of HIIT on V̇O2max. 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 V̇O2max 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 V̇O2max response based on a linear stepwise regression analysis. Results The V̇O2max increased significantly after HIIT (~14%, P < 0.001), but with interindividual differences (−7.8 to 17.9 mL·kg−1·min−1). In 27% of participants, the V̇O2max showed no improvement. We identified one genetic locus near the γ-aminobutyric acid type A receptor subunit beta 3 gene (GABRB3, rs17116985) associated with V̇O2max response at the genome-wide significance level (P < 5 × 10−8), and an additional nine single nucleotide polymorphisms (SNPs) at the suggestive significance level (P < 1 × 10−5). The SNPs rs474377, rs9365605, and rs17116985, respectively, explained 11%, 9%, and 6.2% of variance in V̇O2max response. The 13 SNPs (P < 1 × 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 V̇O2max, sex, and body mass explained 56.4% of the variance in the V̇O2max response; the major predictor was the PPS, which explained 39.4% of the variance. Conclusions The PPS, baseline V̇O2max, sex, and body mass could explain the variance in V̇O2max 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 V̇O2max response.