Sheng, Nan
(2024)
Genome-Wide Association Study of Estimated Fat Mass in Samoan Adults.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Obesity lowers quality of life and is associated with multiple cardiometabolic diseases, including type 2 diabetes (T2D). Excess adiposity affects normal functioning of the pancreas, cardiovascular system, immune system, and alters the balance of certain metabolites. We do not have a complete understanding of all the genetic markers that affect fat mass and how measures of adiposity can be used to predict T2D risk, especially in populations underrepresented in research, such as the Samoan adults in this study. I estimated fat mass and percent body fat in 3,094 participants based on a previously validated equation using age, sex, height, and weight. Next, I performed a genome-wide association study (GWAS) of estimated fat mass of 3,075 participants with complete genetic and phenotypic data across 9,072,005 genetic variants. Finally, since it is challenging to quantify adiposity as a single number, anthropometric measures of adiposity (weight, body mass index, abdominal circumference, hip circumference, abdominal–hip ratio, estimated fat mass, and estimated percent body fat) were examined for their ability to predict T2D risk in 2,885 participants with known T2D status in models that included sex, age, and age² as covariates. The most significant finding of the GWAS were variants in and around CREBRF, consistent with previous studies that this locus is associated with adiposity. The seven adiposity measures performed equivalently as predictors, with abdominal–hip ratio a slightly better predictor in terms of adjusted McFadden pseudo-R², area under the curve, Matthews correlation coefficient, and Akaike information criterion. Information on these genetic markers can play a crucial role in the development of prevention and treatment strategies for the many diseases attributed to obesity. Further studies are still needed to figure out how these variants affect the balance of fat and lean mass and the mechanism of how they change glucose metabolism and T2D risk. If abdominal–hip ratio or estimated fat mass can be used to improve prediction of T2D risk, underresourced communities without specialized equipment could start interventions earlier. Such precision public health approach can potentially reduce the severity of these diseases and improve quality of life for the many people affected.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
27 June 2024 |
| Date Type: |
Publication |
| Defense Date: |
21 May 2024 |
| Approval Date: |
27 June 2024 |
| Submission Date: |
21 June 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
51 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Human Genetics |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
GWAS, Type 2 Diabetes, T2D, Fat Mass, Adiposity, Obesity |
| Date Deposited: |
27 Jun 2024 19:09 |
| Last Modified: |
27 Jun 2024 19:09 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46620 |
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