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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
Kim, Cecilia E.
Witte, Daniel
Sørgjerd, Elin Pettersen
Brillon, David J.
Pedersen, Oluf
Beck-Nielsen, Henning
Grarup, Niels
Pratley, Richard E.
Rickels, Michael R.
Vella, Adrian
Ovalle, Fernando
Melander, Olle
Harris, Ronald I.
Varvel, Stephen
Grill, Valdemar E. R.
Hakonarson, Hakon
Froguel, Philippe
Lonsdale, John T.
Mauricio, Didac
Schloot, Nanette C.
Khunti, Kamlesh
Greenbaum, Carla J.
Åsvold, Bjørn Olav
Yderstræde, Knud B.
Pearson, Ewan R.
Schwartz, Stanley
Voight, Benjamin F.
Hansen, Torben
Tuomi, Tiinamaija
Boehm, Bernhard Otto
Groop, Leif
Leslie, R David
Grant, Struan F. A.
Keywords: Science::Medicine
Issue Date: 2018
Source: Cousminer, D. L., Ahlqvist, E., Mishra, R., Andersen, M. K., Chesi, A., Hawa, M. I., . . . Grant, 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, 41(11), 2396-2403. doi:10.2337/dc18-1032
Journal: Diabetes Care
Abstract: OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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). 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. CONCLUSIONS 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.
ISSN: 0149-5992
DOI: 10.2337/dc18-1032
Rights: © 2018 American Diabetes Association. All rights reserved. This paper was published in Diabetes Care and is made available with permission of American Diabetes Association.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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