NEW YORK (GenomeWeb) – To help accelerate the clinical translation of insights gained from genome-wide association studies (GWAS) in type I diabetes, the National Institutes of Health this month announced that it has earmarked $15 million to fund efforts to characterize and validate genetic variations associated with the disease.
While a number of environmental factors play a role in the development of type I diabetes, a number of studies have also implicated genetics in the disease.
The human leukocyte antigen, or HLA, region of chromosome 6p21.3 has been found to be the strongest genetic determinant for type I diabetes, accounting for up to 50 percent of the genetic risk, according to NIH. Additionally, non-HLA loci including INS, IL2RA, CTLA4, and PTPN22 have been identified through linkage and candidate gene studies.
GWAS have also led to the identification of more than 50 chromosomal regions harboring loci that confer low to moderate risk of developing type 1 diabetes, the agency noted.
A better understanding of the functional consequences of these loci, however, is needed before such discoveries can begin to yield clinical benefits such as reliable biomarkers, new screening strategies, and potentially new therapeutic targets.
Some SNPs identified in GWAS for type I diabetes are correlated with causal variants, while others are located in non-coding regions of the genome, NIH said. Because such variants may influence gene regulatory elements, it will be critical to systematically map transcription factor and microRNA binding sites, chromatin modifications, and expression quantitative trait loci to understand their impact on the initiation and progression of type I diabetes, NIH said.
Meanwhile, the combination of fine-resolution genomic data with gene expression profiles and proteomic data for construction of integrated gene networks is required to understand the pathophysiology of type I diabetes.
Discovering risk genes and their targets could also enable new ways of predicting who will develop type I diabetes, with the examination of these genes and their pathways giving insights into the mechanisms that lead to the autoimmune destruction of insulin-producing beta cells that characterizes the disease.
To that end, NIH is seeking to fund studies aiming to characterize the genetic variations in the genome that have previously been linked to type I diabetes, as well follow-up functional studies of promising genetic variants.
Since different variants may require different approaches to study them, the funding opportunity is not limited to any specific experimental approaches, NIH said.
"For instance, variants in protein-coding region may involve characterization of protein product in vitro, in cell lines, or in transgenic animals," it noted. "The interrogation of variants in non-coding regions may involve the analysis of sequence conservation, expression quantitative loci, and chromatin modifications at regulatory sites."
Research is, however, expected to include human subjects or involve human tissues or cells from well-characterized cohorts, NIH added. "Animal studies, if included, must be complementary to the proposed human research and address mechanistic or therapeutic questions that cannot be addressed directly in humans."
The agency said it will use the $15 million set aside for the funding opportunity to support four to five projects in fiscal 2016. Eligible applicants for the funding include both academic institutions and for-profit organizations.
Applications are due Feb. 17, 2016, with the earliest funded program beginning in Dec. 2016.
Additional information about the funding can be found here.