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- Title
First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes.
- Authors
Cousminer, Diana L.; Ahlqvist, Emma; Mishra, Rajashree; Andersen, Mette K.; Chesi, Alessandra; Hawa, Mohammad I.; Davis, Asa; Hodge, Kenyaita M.; Bradfield, Jonathan P.; Zhou, Kaixin; Guy, Vanessa C.; Åkerlund, Mikael; Wod, Mette; Fritsche, Lars G.; Vestergaard, Henrik; Snyder, James; Højlund, Kurt; Linneberg, Allan; Käräjämäki, Annemari; Brandslund, Ivan
- Abstract
<bold>Objective: </bold>Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.<bold>Research Design and Methods: </bold>We performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10,396).<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
DIABETES complications; AUTOIMMUNE diseases; GENETIC correlations; GLYCOLYSIS; AUTOPHAGY; COMPARATIVE studies; IMMUNITY; INSULIN; TYPE 1 diabetes; RESEARCH methodology; MEDICAL cooperation; TYPE 2 diabetes; RESEARCH; RESEARCH funding; EVALUATION research; CASE-control method; GLUCOSE intolerance; HAPLOTYPES; SEQUENCE analysis
- Publication
Diabetes Care, 2018, Vol 41, Issue 11, p2396
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/dc18-1032