基于全基因组关联分析筛选冬季项目运动员睾酮水平相关遗传标记

梅涛; 李燕春; 杨贤罡; 杨晓琳; 何子红

doi:10.16469/J.css.2025KX011

基于全基因组关联分析筛选冬季项目运动员睾酮水平相关遗传标记

Screening for Genetic Markers Associated with Testosterone Levels in Winter Sports Athletes Based on Genome-Wide Association Analysis

摘要

摘要: 目的：分析冬季项目运动员睾酮水平特征，通过全基因组关联分析（genome-wide association study，GWAS）筛选与冬季项目运动员睾酮水平相关的遗传标记，并采用生物信息学方法分析遗传标记的可能作用机制，以期为冬季项目运动员选材和科学化训练提供依据。方法：以冬季项目运动员作为研究对象（n=456），分析不同水平（普通运动员、精英运动员）运动员睾酮水平的分布和差异。应用PLINKv1.9软件，以冬季项目运动员（n=190）的睾酮水平作为表型变量，性别、年龄以及基因组主成分分析中特征值最大的前5个主成分作为协变量进行GWAS分析，采用3D SNP对纳入模型的单核苷酸多态性位点（single nucleotide polymorphism，SNPs）进行生物功能注释。结果：1）精英运动员的睾酮水平显著高于普通运动员（P＜0.01）。2）男性精英运动员的睾酮水平符合正态分布（P=0.09），睾酮水平范围为14.04～35.65 nmol/L，男性普通运动员睾酮水平符合正态分布（P=0.20），睾酮水平范围为9.270～28.07 nmol/L；女性精英运动员睾酮水平不符合正态分布（P=0.01），睾酮水平范围为0.88～4.44 nmol/L，女性普通运动员睾酮水平符合正态分布（P=0.20），睾酮水平范围为0.19～3.04 nmol/L。3）rs7092867、rs9423319、rs9423320等413个SNPs与睾酮水平显著关联（P＜1×10⁻⁵），其中位于10号染色体ACADSB基因上的6个SNPs（rs7092867、rs9423319、rs9423320、rs9423321、rs9423322、rs9423252）达到了全基因组水平上的显著性（P＜5×10⁻⁸）。4）在冬季项目中，ACADSB基因6个SNPs的aa基因型男性运动员的睾酮浓度显著高于Aa基因型男性运动员（P=0.014），而ACADSB基因6个SNPs的aa基因型女性运动员的睾酮浓度有高于Aa基因型女性运动员的趋势，但未达到统计学意义（P=0.055）。5）3D SNP注释结果显示，6个SNPs在10号染色体上具有共同的3D互作基因（BUB3、C10orf88、HMX2、HMX3、IKZF5、PSTK）。结论：在冬季项目中，精英运动员的睾酮水平高于普通运动员。ACADSB基因上6个SNPs与冬季项目运动员的睾酮水平相关联，aa基因型男性运动员的睾酮浓度高于Aa基因型男性运动员。

Abstract:
Objective : To analyze and screen genetic markers related to testosterone levels in winter sport athletes through genome-wide association studies (GWAS), and explore the potential mechanisms of these genetic markers using bioinformatics methods, so as to provide references for athlete selection and scientific training in winter sports. Methods: 456 winter sport athletes were participated in this study, the distribution and differences in testosterone levels among different level athletes (general athletes and elite athletes) were analyzed. The testosterone levels were set as the phenotypic variable, gender, age, and the top five principal components with the largest eigenvalues from genomic principal component analysis were set as covariates for GWAS analysis of n=190 winter athletes by using PLINKv1.9 software. The 3D SNP tool was employed to annotate the biological functions of the included single nucleotide polymorphism (SNPs).
Results 1) The testosterone levels of elite athletes were significantly higher than those of general athletes (P＜0.01). 2) The testosterone levels of male elite athletes followed a normal distribution (P=0.09), ranging from 14.04 to 35.65 nmol/L, and the male general athletes also followed a normal distribution (P=0.20), ranging from 9.27 to 28.07 nmol/L. For female athletes, the testosterone levels of elite athletes did not follow a normal distribution (P=0.01), with levels ranging from 0.88 to 4.44 nmol/L, whereas those of general athletes followed a normal distribution (P=0.20), with levels ranging from 0.19 to 3.04 nmol/L. 3) A total of 413 SNPs, including rs7092867, rs9423319, and rs9423320, were significantly associated with testosterone levels (P＜1×10⁻⁵). Notably, six SNPs (rs7092867, rs9423319, rs9423320, rs9423321, rs9423322, rs9423252) located on the ACADSB gene on chromosome 10 reached genome-wide significance (P＜5×10⁻⁸). 4) The testosterone concentrations in male athletes with the aa genotype of the six ACADSB SNPs were significantly higher than those with the Aa genotype (P=0.014). Among female winter sport athletes, the testosterone concentrations in the aa genotype were higher than the Aa genotype, but no significant difference was observed (P=0.055). 5) 3D SNP annotation revealed that these six SNPs shared common 3D interaction genes (BUB3, C10orf88, HMX2, HMX3, IKZF5, PSTK) on chromosome 10.
Conclusions Elite winter sport athletes exhibit higher testosterone levels than general athletes. Six novel SNPs on the ACADSB gene were identified to be associated with testosterone levels in winter sport athletes, the male athletes with aa genotype showing higher testosterone concentrations than those with the Aa genotype.

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