dc.contributor.author | Perry, DJ | |
dc.contributor.author | Wasserfall, CH | |
dc.contributor.author | Oram, RA | |
dc.contributor.author | Williams, MD | |
dc.contributor.author | Posgai, A | |
dc.contributor.author | Muir, AB | |
dc.contributor.author | Haller, MJ | |
dc.contributor.author | Schatz, DA | |
dc.contributor.author | Wallet, MA | |
dc.contributor.author | Mathews, CE | |
dc.contributor.author | Atkinson, MA | |
dc.contributor.author | Brusko, TM | |
dc.date.accessioned | 2018-04-30T10:22:18Z | |
dc.date.issued | 2018-03-14 | |
dc.description.abstract | Prior studies identified HLA class-II and 57 additional loci as contributors to genetic susceptibility for type 1 diabetes (T1D). We hypothesized that race and/or ethnicity would be contextually important for evaluating genetic risk markers previously identified from Caucasian/European cohorts. We determined the capacity for a combined genetic risk score (GRS) to discriminate disease-risk subgroups in a racially and ethnically diverse cohort from the southeastern U.S. including 637 T1D patients, 46 at-risk relatives having two or more T1D-related autoantibodies (≥2AAb+), 790 first-degree relatives (≤1AAb+), 68 second-degree relatives (≤1 AAb+), and 405 controls. GRS was higher among Caucasian T1D and at-risk subjects versus ≤ 1AAb+ relatives or controls (P < 0.001). GRS receiver operating characteristic AUC (AUROC) for T1D versus controls was 0.86 (P < 0.001, specificity = 73.9%, sensitivity = 83.3%) among all Caucasian subjects and 0.90 for Hispanic Caucasians (P < 0.001, specificity = 86.5%, sensitivity = 84.4%). Age-at-diagnosis negatively correlated with GRS (P < 0.001) and associated with HLA-DR3/DR4 diplotype. Conversely, GRS was less robust (AUROC = 0.75) and did not correlate with age-of-diagnosis for African Americans. Our findings confirm GRS should be further used in Caucasian populations to assign T1D risk for clinical trials designed for biomarker identification and development of personalized treatment strategies. We also highlight the need to develop a GRS model that accommodates racial diversity. | en_GB |
dc.description.sponsorship | Supported by grants from the National Institutes of Health P01 AI42288 (MAA), R01 DK106191
(TMB), UC4 DK104194 (CEM), and from the JDRF Career Development Award (2–2012–280 to TMB). RAO
is supported by a Diabetes UK Harry Keen Fellowship. DJP is supported by the JDRF Postdoctoral Fellowship
Award (2-PDF-2016-207-A-N). | en_GB |
dc.identifier.citation | Vol. 8: 4529 | en_GB |
dc.identifier.doi | 10.1038/s41598-018-22574-5 | |
dc.identifier.uri | http://hdl.handle.net/10871/32648 | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Publishing Group | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/29540798 | en_GB |
dc.rights | Open Access This article is licensed under a Creative Commons Attribution 4.0 International
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. Te images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons license and your intended use is not permitted
by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the
copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2018 | en_GB |
dc.title | Application of a genetic risk score to racially diverse type 1 diabetes populations demonstrates the need for diversity in risk-modeling | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-04-30T10:22:18Z | |
dc.identifier.issn | 2045-2322 | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the final version of the article. Available from the publisher via the DOI in this record. | en_GB |
dc.identifier.journal | Scientific Reports | en_GB |