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Predicting Body Composition Measurements in Samoan Adults with Multivariate Adaptive Regression Splines and Assessing the Effect of a Missense Variant in CREBRF on Body Composition

Procario, Gregory (2021) Predicting Body Composition Measurements in Samoan Adults with Multivariate Adaptive Regression Splines and Assessing the Effect of a Missense Variant in CREBRF on Body Composition. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Background: The minor A allele of rs373863828, a missense variant in CREBRF that is rare in most populations but common in Samoans, was found to have an association with higher BMI yet lower odds of type 2 diabetes. Identifying the physiological mechanisms behind CREBRF are of paramount importance in the pursuit of understanding obesity.
Methods: Multivariate Adaptive Regression Splines (MARS) models were developed to predict total fat, total lean, and visceral adipose tissue (VAT) mass in a sample of Samoan adults. These models were developed with a subset of the sample (n = 416) who had precise total fat, total lean, and VAT mass measurements; covariates included demographics (sex and age) along with anthropometric measurements (e.g., weight, hip circumference). Mass measurements were imputed from the MARS models for the larger sample (n = 1,970) who lacked total fat, total lean, and VAT mass measurements. These imputed values were applied as outcomes in genetic mixed models that estimated the relationship between rs373863828 and the mass measurements.
Results: MARS models were less optimal in terms of RMSE, R2, and MAE in a majority of the cases, compared to alternative linear regression models. After imputing mass values in the larger sample of Samoans with the MARS models, the sex stratified genetic mixed models were fit. Males and females had higher estimated total fat, total lean, and VAT mass per copy of the A allele ( for males: +1,552.2g, +1,634.9g, and +115.7g, respectively, for females: +1,673.5g, +1,050.0g, and +70.7g, respectively).
Conclusion: The CREBRF variant rs373863828 was associated with higher average mass for all three measurements in Samoan adults, suggesting a broader role of CREBRF in body composition. These effects do not readily explain the paradoxical relationship of this variant with BMI and diabetes. However, our results seem to indicate potential differences by sex in the effects of CREBRF on total fat and total lean mass, that future researchers should investigate.
Public Health Significance: This thesis investigated genetic factors related to obesity in Samoan adults, the results of which may help researchers explicate mechanisms behind the disease.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Procario, Gregorygrp20@pitt.edugrp20
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCarlson, Jennajnc35@ppitt.edujnc35
Committee MemberBuchanich, Jeaninejeanine@pitt.edujeanine
Committee MemberYouk, Adaayouk@pitt.eduayouk
Committee MemberMinster, Ryanrminster@pitt.edurminster
Date: 12 May 2021
Date Type: Publication
Defense Date: 26 April 2021
Approval Date: 12 May 2021
Submission Date: 29 April 2021
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 217
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Biostatistics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: obesity, CREBRF, genetics, Samoa, Multivariate Adaptive Regression Splines, MARS
Date Deposited: 12 May 2021 18:40
Last Modified: 12 May 2021 18:40
URI: http://d-scholarship.pitt.edu/id/eprint/40975

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  • Predicting Body Composition Measurements in Samoan Adults with Multivariate Adaptive Regression Splines and Assessing the Effect of a Missense Variant in CREBRF on Body Composition. (deposited 12 May 2021 18:40) [Currently Displayed]

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