Research Design and Methods: We performed the first genome-wide association study of LADA in cases of European ancestry versus population controls (n = 2,634 vs. 5,947), cases with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10, 396).
Results: The leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring PFKFB3, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1-associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes.
Conclusion: Our results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes, as well as more precise classification strategies.
|Number of pages||7|
|Early online date||22 Oct 2018|
|Publication status||Published - 1 Nov 2018|