Genomic and transcriptomic predictors of triglyceride response to regular exercise

Br J Sports Med. 2015 Dec;49(23):1524-31. doi: 10.1136/bjsports-2015-095179. Epub 2015 Oct 21.


Aim: We performed genome-wide and transcriptome-wide profiling to identify genes and single nucleotide polymorphisms (SNPs) associated with the response of triglycerides (TG) to exercise training.

Methods: Plasma TG levels were measured before and after a 20-week endurance training programme in 478 white participants from the HERITAGE Family Study. Illumina HumanCNV370-Quad v3.0 BeadChips were genotyped using the Illumina BeadStation 500GX platform. Affymetrix HG-U133+2 arrays were used to quantitate gene expression levels from baseline muscle biopsies of a subset of participants (N=52). Genome-wide association study (GWAS) analysis was performed using MERLIN, while transcriptomic predictor models were developed using the R-package GALGO.

Results: The GWAS results showed that eight SNPs were associated with TG training-response (ΔTG) at p<9.9×10(-6), while another 31 SNPs showed p values <1×10(-4). In multivariate regression models, the top 10 SNPs explained 32.0% of the variance in ΔTG, while conditional heritability analysis showed that four SNPs statistically accounted for all of the heritability of ΔTG. A molecular signature based on the baseline expression of 11 genes predicted 27% of ΔTG in HERITAGE, which was validated in an independent study. A composite SNP score based on the top four SNPs, each from the genomic and transcriptomic analyses, was the strongest predictor of ΔTG (R(2)=0.14, p=3.0×10(-68)).

Conclusions: Our results indicate that skeletal muscle transcript abundance at 11 genes and SNPs at a number of loci contribute to TG response to exercise training. Combining data from genomics and transcriptomics analyses identified a SNP-based gene signature that should be further tested in independent samples.

Keywords: Exercise; Intervention; Lipids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Exercise / physiology*
  • Genome-Wide Association Study
  • Genomics
  • Genotype
  • Humans
  • Middle Aged
  • Muscle, Skeletal / physiology
  • Polymorphism, Single Nucleotide / genetics
  • RNA / genetics
  • Transcriptome
  • Triglycerides / metabolism*
  • Young Adult


  • Triglycerides
  • RNA