A transcript-wide association study in physical activity intervention implicates molecular pathways in chronic disease

BackgroundPhysical activity is associated with decreased risk for several chronic and acute conditions including obesity, diabetes, cardiovascular disease, mental health and aging. However, the biological mechanisms associated with this decreased risk are elusive. One way to ascertain biological changes influenced by physical activity is by monitoring changes in how genes are expressed. In this investigation, we conducted a transcriptome-wide association study of physical activity, meta-analyzing 20 independent studies to increase power for discovery of genes expressed before and after physical activity. Further, we hypothesize that genes identified in physical activity are expressed in obesity, inflammation, major depressive disorder and healthy aging.\n\nResultsOur analysis identified thirty (30) transcripts induced by physical activity (PA signature), at an FDR < 0.05. Twenty (20) of these transcripts, including COL4A3, CAMKD1, SLC4A5, EPS15L1, RBM33, and CACNG1, are up-regulated and ten (10) transcripts including CRY1, ZNF346, SDF4, ANXA1 and YWHAZ are down-regulated. We find that several of these physical activity transcripts are associated and biologically concordant in direction with body mass index, white blood cell count, and healthy aging.\n\nConclusionspowerful approach, we found thirty genes that were putatively influenced by physical activity, eight of which are inversely associated with body mass index, thirteen inversely associated with white blood cell count, and three associated and concordant with healthy aging. One gene was significant and concordant with major depressive disorder. These results highlight the potential molecular basis for the protective benefit of physical activity for a broad set of chronic conditions.