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Utility of CREBRF genotype with BMI in prediction of type 2 diabetes

Tiner, Jessica (2020) Utility of CREBRF genotype with BMI in prediction of type 2 diabetes. Master Essay, University of Pittsburgh.

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Type 2 diabetes (T2D) is a major global health concern which particularly affects Sa-moans, who have high rates of obesity (66% of women and 45% of men) and, as a result, face high rates of obesity-related morbidities including diabetes. In Samoa in 2013, 23% of women and 21% of men were diabetic. The minor allele of a common genetic variant in Samoans, rs373863828 (CREBRF:p.R457Q) has been associated with a 1.6-fold lower risk of T2D. The American Diabetes Association recommends screening adults for T2D when their BMI is >25 kg/m2. This BMI action point might be inappropriate for Samoans and more precise values may be determined using genetic information. Here we determine how the addition of CREBRF genotype affects the usefulness of BMI in predicting T2D status in Samoans. We used receiver operating characteristic (ROC) curves analysis to assess the utility of BMI with and without the genotype in predicting diabetes status, BMI action points and specificity at 80% sensitivity, in men and women, both overall and by genotype group. In females, the 80% sensitivity action points for BMI were 30.3 kg/m2 overall (with 27% specificity), 30.3 kg/m2 for GG (30%), 31.4 kg/m2 for GA (30%), and 29.7 kg/m2 for AA (17%). In men, they were 28.7 kg/m2 overall (with 40% specificity), 27.8 kg/m2 for GG (39%), 30.6 kg/m2 for GA (48%), and 32.2 kg/m2 for AA (57%). These analyses show that higher Samoan-specific screening thresholds are merited, and that the addition of the CREBRF genotype does not usefully alter the ability of BMI to predict T2D as assessed by examining the change in the AUC. However, 80% sensitivity threshold val-ues by genotype suggest that including CREBRF genotype may be beneficial over BMI alone, by improving specificity without loss of sensitivity. This benefit needs to be weighed nonethe-less against the costs of genotyping for this variant. The public health significance of this study is that it illustrates the need for stronger T2D screening and prevention outreach in Samoa. In addition, it supports the creation of higher, Samoan-specific BMI action points to be used for T2D screening.


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Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Tiner, JessicaJCT46@pitt.edujct46
ContributionContributors NameEmailPitt UsernameORCID
Committee ChairMinster, Ryanrminster@pitt.eduUNSPECIFIEDUNSPECIFIED
Committee MemberKammerer, Candacecmk3@pitt.eduUNSPECIFIEDUNSPECIFIED
Committee MemberCarlson, Jennajnc35@pitt.eduUNSPECIFIEDUNSPECIFIED
Date: 5 May 2020
Date Type: Submission
Number of Pages: 47
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Date Deposited: 02 Sep 2020 21:34
Last Modified: 01 May 2022 05:15

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