Genome-wide assessment reveals a significant association between ACSS3 and physical activity

Recent genetic studies have identified physical activity (PA)-susceptible loci in European ancestry subjects; however, due to considerable genetic differences, these findings are not likely extendable to East Asian populations. Therefore, the present study aimed to identify significantly associated PA-susceptible loci using genome-wide association studies (GWASs) with East Asian (EAS) subjects and to generalize the findings to European (EUR) ancestries. The mRNA levels of genes located near the genome-wide significantly associated single-nucleotide polymorphisms (SNP) were compared under PA and control conditions. Rs74937256, located in ACSS3 (chromosome 12), which primarily functions in skeletal muscle tissues, was identified as a genome-wide significant variant (P = 6.06 × 10⁻⁹) in EAS. Additionally, the rs2525840, also in ACSS3 satisfied the Bonferroni corrected significance (P = 3.77 × 10⁻⁵) in EUR. We found that rs74937256 is an expressed trait locus of ACSS3 (P = 10⁻⁴), and ACSS3 mRNA expression significantly differs after PA, based on PrediXcan (P = 7 × 10⁻⁸) and the gene expression omnibus database (P = 0.043).