Using DNA Methylation Markers To Predict Clinically Important Traits In Mammals
SUMMARY
UCLA researchers in the Department of Molecular, Cell, and Developmental Biology have found association of DNA methylation with metabolic syndrome traits in human adipose tissue samples using epigenome-wide association studies (EWAS).
BACKGROUND
The genome-wide association study (GWAS) approach, which involves comparing genetic variants in large numbers of individuals that have the disease versus those that do not, made it possible in identifying some of the genetic factors that underlie common complex diseases such as diabetes, obesity, hypertension, and cancer. Similar to GWAS, EWAS aims to identify candidate genes for traits by using epigenetic factors instead of single-nucleotide polymorphism genotypes in the association model. Epigenome-wide association studies have recently identified associations for complex traits such as bone mineral density, obesity, and insulin resistance in mice.
Methylation of DNA cytosine bases is evolutionarily conserved and plays important roles in development, cell differentiation, imprinting, X-chromosome inactivation, and regulation of gene expression. However, environmental factors, such as diet and smoking, and stochastic factors can alter DNA methylation profiles, resulting in aberrant DNA methylation marks. Aberrant DNA methylation in mammals is associated with both rare and complex traits including cancer, aging, and imprinting disorders. DNA methylation states have also been shown to be associated with biological processes underlying metabolic syndrome, including obesity, hypertension, and diabetes.
INNOVATION
Researchers at UCLA have utilized natural variation in DNA methylation in a human population to explore the relationship between DNA methylation and complex clinical traits. Epigenome-wide association studies were performed on clinical traits using reduced representation bisulfite sequencing data and identified 61 significant associations for metabolic syndrome traits. These associations include previously known genes, as well as novel candidate genes associated with diabetes and obesity phenotypes in humans. These studies were carried out in adipose tissue, and not blood, differentiating it from previous studies.
APPLICATIONS
- The newly identified DNA methylation markers can be used to predict clinically important aspects such as heart failure, potentially for metabolic disorders, etc.
ADVANTAGES
- EWAS studies using DNA methylation gives more accurate predictions of phenotype than GWAS
- Studies were carried out in adipose tissue samples
STATE OF DEVELOPMENT
The EWAS method has been developed and tested on 201 adipose tissue samples from the Metabolic Syndrome in Men (METSIM) cohort.
RELATED MATERIALS
Orozco, L.D., Farrell, C., Hale, C., Rubbi, L., Rinaldi, A., Civelek, M., Pan, C., Lam, L., Montoya, D., Edillor, C., Seldin, M., Boehnke, M., Mohlke, K.L., Jacobsen, S., Kuusisto, J., Laakso, M., Lusis, A.J., and Pellegrini, M., Epigenome-wide association in adipose tissue from the METSIM cohort, Hum. Mol. Genet., 2018.