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).