基于全基因组关联分析的青年人群卧推1RM抗阻训练效果预测模型研究
Prediction Model of Bench Press 1RM Resistance Training Effect in Young People Based on GWAS
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摘要: 目的:通过全基因组关联分析(genome-wide association studies,GWAS)筛选卧推1RM抗阻训练效果相关遗传标记,联合表型指标构建卧推1RM抗阻训练效果预测模型,并采用生物信息学方法分析遗传标记的可能作用机制,以期为制定精准化的运动健身指导方案提供依据。方法:193名非规律运动成年人完成12周抗阻力量训练,训练干预前后测试卧推1RM、身体成分、肌肉厚度等表型指标。采集受试者DNA,利用Illumina Infinium CGA-24v1-0芯片进行全基因组基因型解析。应用PLINK1.9软件进行GWAS分析,并筛选卧推1RM训练效果相关单核苷酸多态性位点(single-nucleotide polymorphisms,SNPs)。采用平均值法计算权重后的基因组多基因得分(genomics polygenic scores,GPGS),采用K-mean方法对卧推1RM变化百分比进行聚类分析,采用前进法Logistic回归分析建立以基因组-表型指标为预测因子的卧推1RM训练效果综合预测模型,采用HaploReg v4.1、GTEx、KEGG对纳入模型的SNPs进行生物功能注释。结果:1)12周抗阻训练后,卧推1RM平均提高36.25%(P<0.01),个体差异变化范围为-31.25%~176.92%;2)GWAS显示35个SNPs与卧推1RM抗阻训练效果显著关联(P<1×10-6),7个SNPs被纳入基因组学回归模型,可解释训练效果个体差异的39.6%,其中rs79726572、rs112183859、rs77187527的解释度分别为13.7%、9%、8%;权重后的GPGS平均得分为3.12,变化范围为-3.93~27.21;3)联合GPGS与表型指标构建的综合模型,卧推初始值、BMI、右上肢肌肉质量、左躯干肌肉质量、GPGS得分被纳入综合模型(AUC为0.952,约登指数0.767,cut off值0.251);4)生物信息学分析表明,卧推1RM训练效果基因组预测模型中的7个SNPs所在基因或受调控基因功能与肌生成等相关;受调控的基因富集于Generic Transcription Pathway、Developmental Biology、Myogenesis等37条信号通路(P<0.01,FDR<0.01)。结论:首次基于GWAS筛选出rs79726572、rs112183859、rs77187527等7个与卧推1RM训练效果相关的遗传标记。建立的基因组-表型综合预测模型对卧推1RM训练效果具有较好的预测能力。卧推1RM训练效果相关的SNPs与骨骼肌生长发育生物过程相关,其中Myogenesis信号通路是值得注意的一条通路。Abstract: Objective: The genome-wide association analysis(GWAS) was used to screen genetic markers associated with resistance training effects of bench press 1RM, then a predictive model of bench press 1RM resistance training effect was constructed by combining with phenotye indicators; in addition, the bioinformatics was used to analyze the possible mechanisms of genetic markers in order to provide references for formulate precise exercise and fitness programs. Methods: 193 non-regular exercise adults completed a 12-week resistance training program, the phenotypic indicators such as bench press 1RM, body composition, and muscle thickness were tested before and after the training intervention. The subjects' DNA was collected, and whole-genome genotyping analysis was performed using the Illumina Infinium CGA-24v1-0 chip. GWAS analysis was conducted using PLINK1.9software, and single-nucleotide polymorphisms(SNPs) affecting bench press 1RM training effect were screened. The mean method was used to calculate the genomics polygenic scores(GPGS) after weighting. The K-mean method was used to cluster the percentage change in bench press 1RM and the forward logistic regression analysis was used to build a comprehensive model for predicting the training effect of genomic-phenotye indicators. HaploReg v4.1, GTEx, and KEGG were used to annotate the SNPs included in the model for biofunctionality. Results: 1) After 12 weeks of resistance training, the mean improvement in bench press 1RM was 36.25%(P<0.01), but the individual variation was significant which was ranging from-31.25% to 176.92%. 2) GWAS showed 35 SNPs were significantly associated with the effect of bench press 1RM resistance training(P<1×10-6), and 7 SNPs were included in the genomics regression model to explain 39.6% of the individual differences in training effect, with rs79726572,rs112183859 and rs77187527 explaining 13.7%, 9% and 8%, respectively; the mean GPGS score after weighting was 3.12(range of variation:-3.93 to 27.21). 3) The initial values of prone push, BMI, right upper limb muscle mass, left trunk muscle mass, and GPGS scores were included in the combined model which was constructed by GPGS and phenotype indicators(AUC=0.952, Jorden index=0.767, cut off value 0.251). 4) Bioinformatic analyses showed that the genes or regulated genes underlying 7 SNPs in the genomic prediction model of bench press 1RM training effect were functionally associated with myogenesis; the regulated genes were enriched in Generic Transcription Pathway, Developmental Biology, Myogenesis and other 37 pathways(P<0.01, FDR<0.01). Conclusions: It is the first study to find 7 genetic markers(rs79726572, rs112183859, rs77187527, etc.) related to bench press 1RM training effect based on GWAS. The established “genome-phenotype” comprehensive prediction model has good predictive ability for bench press 1RM training effect. The SNPs related to bench press 1RM training effect are associated with the biological processes of skeletal muscle growth and development, among which the Myogenesis signaling pathway is worth noting.