Allele Frequency Distribution and Population Differentiation of Athletic Performance‑ Associated Polymorphisms (ACTN3, ACE, PPARGC1A) in Southeast Asian Populations
Fixation Index (FST) and Total Genotype Score (TGS) Analysis Using the 1000 Genomes Project
DOI:
https://doi.org/10.21831/jomassh.v2i2.2836Keywords:
FST, Performance‑Associated Polymorphisms, sports genomics, Total Genotype ScoreAbstract
Background. Athletic performance genomics is dominated by studies conducted in European and African populations, leaving Southeast Asian (SEA) populations systematically underrepresented. The three most extensively studied performance‑associated polymorphisms—ACTN3 rs1815739 (R577X), ACE insertion/deletion (proxied by rs4341), and PPARGC1A rs8192678 (Gly482Ser), remain poorly characterized in SEA populations at the population‑genetics level. While individual loci have been examined in adjacent East Asian cohorts (primarily Japanese, Korean, and Han Chinese), no prior study has jointly reported all three loci alongside FST and TGS analyses specifically for KHV or CDX populations, to the best of our knowledge. Objectives. This study aims to characterise the allele and genotype frequencies of ACTN3 rs1815739, ACE rs4341, and PPARGC1A rs8192678 in the Kinh Vietnamese (KHV) and Chinese Dai (CDX) populations, quantify their population differentiation relative to other continental superpopulations, evaluate the applicability of a European-calibrated Total Genotype Score framework in SEA populations, and assess the practical significance of ACE allele directionality reversal for endurance genomic scoring in the region. Methods. We performed a descriptive bioinformatics analysis of phased genotype data from the 1000 Genomes Project Phase 3 (n = 2,503 individuals, 26 populations). Allele frequencies with 95 % Wilson confidence intervals, Hardy–Weinberg Equilibrium (HWE) exact tests, global and pairwise FST, chi‑square tests with Bonferroni correction, and a Total Genotype Score (TGS) framework were applied. Results. SEA populations (Kinh Vietnamese [KHV], n = 99; Chinese Dai [CDX], n = 93) showed intermediate ACTN3 alt‑allele frequencies (KHV: 0.409; CDX: 0.505), high ACE rs4341 C‑ allele frequencies (KHV: 0.672; CDX: 0.656), and intermediate PPARGC1A frequencies (KHV: 0.450; CDX: 0.430). Global FST was highest for ACTN3 (FST = 0.151, high differentiation). Under the European‑calibrated TGS framework SEA scored significantly below EUR reference for TGS En‑ durance (∆ = −16.7 points for KHV; Mann–Whitney p = 6.23 × 10−14), but not for TGS Power (p = 0.527). Reversing ACE directionality per the EAS model increased TGS Endurance by +17.2 (KHV) and +15.6 (CDX) points. Conclusions. SEA populations show distinct allele frequency profiles from European reference populations, driven by PPARGC1A differentiation versus African populations (FST = 0.234) and ACE directionality ambiguity. These findings provide, to the best of our knowledge, the first joint population‑genetic characterization of these three loci with concurrent FST and TGS analysis specifically for the KHV and CDX populations, and highlight systematic limitations of European‑calibrated TGS frameworks when applied to non‑European populations.
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