NIH Research Festival
Aging is a major contributing risk factor for age-related diseases. The complex interplay of genetics, environment, and stochasticity alters local accessibility and regulation of genetic information, resulting in transcriptomic dysregulations. Although GWAS of age-related diseases have suggested genes and pathways contributing to pathophysiology, the effects of aging in these study designs are challenging to account for and are often forgone when using age as a covariate. QTL are genomic regions statistically correlated with traits (e.g., GE/mCpGs) and are largely non-coding regulatory sites that mediate changes in gene expression. We hypothesize that aging-associated gene expression changes are determined, at least in part, by genetic variations and epigenetic changes resulting from environmental factors and lifestyle. We present a novel framework to study the effect of aging in age-related diseases by longitudinally characterizing the physiologic aging of the retina by integrating diverse ‚Äúomics‚Äù datasets across the lifespan. First, we modeled GE changes across age with linear and non-linear regression to identify age-related differential GE. Secondly, we will establish retinal QTLs (eQTL, mQTL) to study natural genetic variations‚Äô impact on expression and methylation. With the QTLs, we (1) dissect genetic variation in GE/mCpGs with QTLs accounting for aging and natural variability of genetic polymorphism on GE/mCpGs; (2) explore GE/mCpGs effect on aging by analyzing the differential GE and methylated regions by comparing across the lifespan; and (3) distinguish the role of epigenetics in transcriptome by integrating the GE and mCpGs associated with aging with eQTM to capture the dynamics of epigenetic in the transcriptome.
Scientific Focus Area: Genetics and Genomics
This page was last updated on Monday, September 25, 2023