Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC

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Bibtex

@article{e8e5d5937bc64368a332aa380c99eadc,
title = "Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC",
abstract = "OBJECTIVE: The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS: Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS: The strongest associations in the MHC class II region (rs3957146, β [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (β [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, β [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS: In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.",
author = "Rajashree Mishra and Mikael {\AA}kerlund and Cousminer, {Diana L.} and Emma Ahlqvist and Bradfield, {Jonathan P.} and Alessandra Chesi and Hodge, {Kenyaita M.} and Guy, {Vanessa C.} and Brillon, {David J.} and Pratley, {Richard E.} and Rickels, {Michael R.} and Adrian Vella and Fernando Ovalle and Harris, {Ronald I.} and Olle Melander and Stephen Varvel and Hakon Hakonarson and Phillippe Froguel and Lonsdale, {John T.} and Didac Mauricio and Schloot, {Nanette C.} and Kamlesh Khunti and Greenbaum, {Carla J.} and Yderstr{\ae}de, {Knud B.} and Tiinamaija Tuomi and Voight, {Benjamin F.} and Stanley Schwartz and Boehm, {Bernhard O.} and Leif Groop and Leslie, {Richard David} and Grant, {Struan F.A.}",
year = "2020",
doi = "10.2337/dc19-0986",
language = "English",
volume = "43",
pages = "418--425",
journal = "Diabetes Reviews",
issn = "1935-5548",
publisher = "American Diabetes Association",
number = "2",

}