Abstract
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).
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