First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes

Show full item record



Permalink

http://hdl.handle.net/10138/306614

Citation

Bone Mineral Density Childhood , Groop , L , Leslie , R D & Gran , S F A 2018 , ' First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes ' , Diabetes Care , vol. 41 , no. 11 , pp. 2396-2403 . https://doi.org/10.2337/dc18-1032

Title: First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes
Author: Bone Mineral Density Childhood; Groop, Leif; Leslie, R. David; Gran, Struan F.A.
Contributor: University of Helsinki, Centre of Excellence in Complex Disease Genetics
Date: 2018-11
Language: eng
Number of pages: 8
Belongs to series: Diabetes Care
ISSN: 0149-5992
URI: http://hdl.handle.net/10138/306614
Abstract: OBJECTIVELatent 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.RESEARCH DESIGN AND METHODSWe 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).RESULTSThe 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.CONCLUSIONSOur results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.
Subject: INDUCIBLE 6-PHOSPHOFRUCTO-2-KINASE
GENETIC ARCHITECTURE
INSULIN-RESISTANCE
TYPE-1
ONSET
PHENOTYPE
LADA
VARIANTS
LOCI
FREQUENCY
3121 General medicine, internal medicine and other clinical medicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
2396.full.pdf 824.3Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record