Several recent studies are contributing to understanding the genetic underpinnings of type 1 diabetes. Scientists in the NIDDK-supported Type 1 Diabetes Genetics Consortium (T1DCG) studied over 2,400 families and discovered that variants in the UBASH3A genetic region were associated with the disease. They also confirmed previously reported associations with three other genetic regions (INS, IFIH1, and KIAA0305). A study by a different group of scientists analyzed several patient populations to follow-up on results of recent genome-wide association studies (GWAS). These populations included people enrolled in the T1DGC, as well as participants from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study, which is a long-term NIDDK-supported study of people with type 1 diabetes. These researchers also identified UBASH3A as being associated with type 1 diabetes, and in addition discovered an association in the BACH2 genetic region. UBASH3A is predominantly found in immune system cells called T cells, and BACH2 is thought to be a regulator of the immune system’s antibody response. Because type 1 diabetes is an autoimmune disease, it is plausible that defects in these genes could contribute to type 1 diabetes, although more research will help determine how these genes may play a role. In another study, scientists examined an independent patient population to confirm the association between variants in the IFIH1 genetic region and type 1 diabetes. The IFIH1 gene was found to be more strongly expressed (turned on) in some immune system cells from people carrying variants of the gene associated with type 1 diabetes. This observation suggests that higher amounts of the protein encoded by the IFIH1 gene may be linked to increased risk for type 1 diabetes, but additional studies in more people are necessary to confirm the finding. IFIH1 is thought to play a role in the immune system and has also been linked to two other autoimmune diseases. In another study, T1DGC scientists combined data from a new GWAS with data from previous studies to discover that over 40 different genetic regions influence a person’s risk of developing type 1 diabetes. That number includes the genetic regions described above, as well as several novel regions.
Scientists are also building on recent genetics findings to understand how other genetic factors contribute to risk for type 1 diabetes. Researchers looked at previously-identified type 1 diabetes susceptibility genes to determine their impact on an early stage in type 1 diabetes onset—the development of autoimmunity—in children participating in the NIDDK-supported Diabetes Autoimmunity Study in the Young (DAISY). These children were originally enrolled in DAISY because they carry variants for a different diabetes susceptibility gene (HLA) that put them at high genetic risk for developing type 1 diabetes. The scientists discovered that a variant in the PTPN22 gene region increased the risk of developing autoimmunity in children with a family history of the disease. In contrast, a variant of the CTLA-4 gene region increased the risk of autoimmunity in children without such a family history.
These studies are shedding new light on genetic factors that underlie type 1 diabetes, and may lead to enhanced ways to predict who is at high risk for the disease, and potentially inform new intervention approaches. They also demonstrate how new knowledge is stemming from long-term, NIDDK-supported research studies based on new and emerging genetics technologies.
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