Qian, Chenao
(2021)
Genome-wide association studies in Samoans give insight into obesity by investigating skinfold thickness.
Master's Thesis, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
In the last 30 years, Samoan people have experienced increasing high levels of obesity and associated diseases. While modernization and consequent lifestyle changes contribute to the prevalence of obesity, there is strong evidence that genetic variation is associated with adiposity and cardiometabolic risk factors in Samoans. Current studies mainly use body mass index (BMI) to understand obesity; limited effort has focused on skinfold measurements.
In this study, we performed genome-wide association studies of five skinfolds: Triceps, Forearm, Subscapular, Abdominal, and Suprailiac, while appropriately handling the beyond-detection-limit values in skinfold measurements. The sample contains 3,072 participants from the Independent State of Samoa. 659,492 variants were genotyped on an Affymetrix 6.0 array and then an additional 9,619,694 variants were imputed using a Samoan-specific haplotype reference panel derived from 1,284 Samoan individuals whole-genome sequenced through the TOPMed program. We tested five skinfolds for association via sex-stratified Cox mixed-effects models as implemented in COXMEG, while adjusting for fixed effects of age, with or without BMI, and a kinship random effect.
We identified two genome-wide significant loci after adjusting for multiple testing ( P<5×10^(-8)÷3). The top variants at each peak are rs980493892 (P=4.03×10^(-17)) and rs198537 (P=6.36×10^(-13)), associated with forearm skinfold in female participants. For rs980493892, GG homozygotes have higher skinfold thickness compared to T allele carriers, with the estimated effect size of 0.45 per copy of the effect allele. This variant is extremely rare in other populations, but common in Samoan population (minor allele frequency (MAF) = 0.152). Three genes near this peak are TSEN2, PPARG, RAF1, which are associated with body fat percentage, waist-to-hip ratio, and type 2 diabetes. A similar pattern is observed for rs198537 (MAF = 0.185), with the estimated effect size of 0.37 per copy of the effect allele. The closest genes include CACNA1G-AS1, SPATA20, MYCBPAP, EPN3. No research has looked into their associations with obesity yet. This study is important to public health because it can help better understanding the inherited basis and biological mechanism of obesity, which may reveal previously unknown biological mechanisms of obesity.
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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: |
19 January 2021 |
| Date Type: |
Publication |
| Defense Date: |
25 November 2020 |
| Approval Date: |
19 January 2021 |
| Submission Date: |
5 December 2020 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
68 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Biostatistics |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Samoan, Obesity, Skinfolds, GWAS, Beyond-detection-limit values, Cox mixed-effects models |
| Date Deposited: |
19 Jan 2021 19:48 |
| Last Modified: |
19 Jan 2023 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/40098 |
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Genome-wide association studies in Samoans give insight into obesity by investigating skinfold thickness. (deposited 19 Jan 2021 19:48)
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