CHAPEL HILL – Thousands of DNA variants may contribute to common diseases by affecting how well a gene is expressed, but the identity of these variants is unknown. To address this problem, The National Institutes of Health is providing approximately $185 million over five years to the Impact of Genomic Variation on Function (IGVF) consortium composed of 25 awards across 30 U.S. research sites. IGVF consortium investigators will work to understand how genomic variation alters human genome function, and how such variation influences human health and disease.

The proposed UNC-led $9.25 million study over five years, spearheaded by Hyejung Won, PhD, assistant professor in the UNC Department of Genetics, will identify specific DNA variants that alter gene expression level to influence risk of disease. The study will determine whether variants act differently in males and females; in the brain, liver, muscle, lung, and heart; and in or out of an inflamed environment.

“As members of the IGVF Consortium, we will also generate a regulatory variant catalog for the community, and enable future studies through data collection and predictive models,” said Won, who is a member of the UNC Neuroscience Center. “The ultimate goal of the IGVF is to identify new targets to treat common diseases.”

Karen Mohlke, PhD
Karen Mohlke, PhD

Co-investigators at UNC-Chapel Hill are Karen Mohlke, PhD, professor of genetics at the UNC School of Medicine, and Michael Love, PhD, assistant professor of genetics and biostatistics at the UNC Gillings School of Global Public Health.

Thousands of genetic loci – specific locations on chromosomes – are associated with human traits or disease risk, and these loci each typically contain tens to hundreds of variants, most of which are non-coding and lack direct evidence of effects on genes. Experimental tests of genomic variants are needed to identify functional effects, which can be specific to one sex, tissue, and/or perturbed environmental contexts, such as inflammation, a hallmark disease state.

“The expertise of the study investigators in genome-wide association studies, statistical and computational genetics, human genomics, AAV delivery (gene therapy), and mouse physiology make achievement of these aims feasible and likely highly informative to understand how genomic variation impacts human health and disease,” Won said.

© University of North Carolina at Chapel Hill