Fetal programming and parent of origin effects on type 2 diabetes and insulin secretion

Type 2 diabetes (T2D) is a lifelong disabling disease, characterized by deficient insulin secretion due to pancreatic ß-cell dysfunction combined with insulin resistance in later life. Diabetes is the fastest increasing disease with an estimated prevalence of 1/8 adult living with diabetes in 2045.

T2D is a consequence of a complex interplay between environment, genetics and epigenetics. The environmental risk factors for T2D are well known, with obesity being the predominant one. However, it is also well established that there is a strong hereditary component.

While over 1000 loci has been documented for their involvement in T2D pathogenesis, they only explain approx. 20% of the heritability leaving the larger parts of the picture unexplained. Parent of origin effects (POE) is well documented in certain other conditions such as genetic imprinting, but so far POE has not been very much studied in T2D. Therefore, we hypothesize that investigating POE in T2D may potentially uncover previously unknown parts of the heritability and partly explain the increased transmission of T2D from mothers to offspring. In this study, we aim to identify novel genes showing POE with special focus on genes associated with insulin secretion.