Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC.
dc.contributor.author | Mishra, R | en_US |
dc.contributor.author | Åkerlund, M | en_US |
dc.contributor.author | Cousminer, DL | en_US |
dc.contributor.author | Ahlqvist, E | en_US |
dc.contributor.author | Bradfield, JP | en_US |
dc.contributor.author | Chesi, A | en_US |
dc.contributor.author | Hodge, KM | en_US |
dc.contributor.author | Guy, VC | en_US |
dc.contributor.author | Brillon, DJ | en_US |
dc.contributor.author | Pratley, RE | en_US |
dc.contributor.author | Rickels, MR | en_US |
dc.contributor.author | Vella, A | en_US |
dc.contributor.author | Ovalle, F | en_US |
dc.contributor.author | Harris, RI | en_US |
dc.contributor.author | Melander, O | en_US |
dc.contributor.author | Varvel, S | en_US |
dc.contributor.author | Hakonarson, H | en_US |
dc.contributor.author | Froguel, P | en_US |
dc.contributor.author | Lonsdale, JT | en_US |
dc.contributor.author | Mauricio, D | en_US |
dc.contributor.author | Schloot, NC | en_US |
dc.contributor.author | Khunti, K | en_US |
dc.contributor.author | Greenbaum, CJ | en_US |
dc.contributor.author | Yderstræde, KB | en_US |
dc.contributor.author | Tuomi, T | en_US |
dc.contributor.author | Voight, BF | en_US |
dc.contributor.author | Schwartz, S | en_US |
dc.contributor.author | Boehm, BO | en_US |
dc.contributor.author | Groop, L | en_US |
dc.contributor.author | Leslie, RD | en_US |
dc.contributor.author | Grant, SFA | en_US |
dc.date.accessioned | 2020-01-07T09:40:15Z | |
dc.date.available | 2019-11-16 | en_US |
dc.date.issued | 2020-02 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/62219 | |
dc.description.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. | en_US |
dc.format.extent | 418 - 425 | en_US |
dc.format.medium | Print-Electronic | |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Diabetes Care | en_US |
dc.title | Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.2337/dc19-0986 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/31843946 | en_US |
pubs.issue | 2 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 43 | en_US |
dcterms.dateAccepted | 2019-11-16 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
qmul.funder | Prevalence and Characterisation of Latent Autoimmune Diabetes in Adults (LADA) across Europe (ACTION LADA)::European Union FP5 European Commission Research Directorates | en_US |
Files in this item
This item appears in the following Collection(s)
-
Centre for Immunobiology [1122]