Environmental and genetic contribution to the risk of T2D in the United Arab Emirates
File(s)
Author(s)
Alkaf, Budour
Type
Thesis
Abstract
Background
Type 2 diabetes (T2D) has emerged as a major healthcare problem at a global level. Populations in the Arabian Peninsula, including Arab-Emiratis, are repeatedly reported to have some of the highest rates of T2D. I aimed to investigate the contribution of lifestyle and genetic risk factors to this increased burden, that is yet to be determined.
Methods
I analysed publicly-available worldwide estimates to assess the contribution of obesity and physical inactivity towards differences in overall diabetes rates across populations. I investigated two Arab-Emirati sample populations to examine the contribution of adiposity and physical inactivity towards T2D risk, as compared to individuals of Caucasian, South Asian and Afro-Caribbean descent from the UK Biobank study. I performed a genome-wide association study in 1,200 Arab-Emiratis to identify known and novel genetic factors underlying T2D in the population.
Results
Populations experiencing similar environmental shifts are differentially subject to T2D risk. Arab-Emiratis have a 13-fold excess risk of T2D compared to Europeans, independent of BMI. There is a stronger association of central adiposity towards T2D risk in Arab-Emiratis compared to other ethnic groups. Sedentary time explains a bigger proportion of T2D risk compared to overall physical inactivity in Arab-Emiratis. I identified 40 novel loci in association with T2D (P-value < 5x10-6), with one loci reaching genome-wide significance mapping to MALRD1 (P-value = 1.6x10-8). Overall, results showed that previously reported T2D risk loci cannot fully account for the increased risk in Arab-Emiratis.
Conclusions
Increased T2D risk in Arab-Emiratis could be more attributable to central adiposity rather than BMI. Findings highlighted the negative impact of physical inactivity on insulin resistance and central adiposity in Arab-Emiratis, but its contribution towards their increased T2D risk is limited. Lastly, I identified 40 novel loci for T2D that potentially provide further insight into the genetic mechanisms underlying T2D in Arab-Emiratis.
Type 2 diabetes (T2D) has emerged as a major healthcare problem at a global level. Populations in the Arabian Peninsula, including Arab-Emiratis, are repeatedly reported to have some of the highest rates of T2D. I aimed to investigate the contribution of lifestyle and genetic risk factors to this increased burden, that is yet to be determined.
Methods
I analysed publicly-available worldwide estimates to assess the contribution of obesity and physical inactivity towards differences in overall diabetes rates across populations. I investigated two Arab-Emirati sample populations to examine the contribution of adiposity and physical inactivity towards T2D risk, as compared to individuals of Caucasian, South Asian and Afro-Caribbean descent from the UK Biobank study. I performed a genome-wide association study in 1,200 Arab-Emiratis to identify known and novel genetic factors underlying T2D in the population.
Results
Populations experiencing similar environmental shifts are differentially subject to T2D risk. Arab-Emiratis have a 13-fold excess risk of T2D compared to Europeans, independent of BMI. There is a stronger association of central adiposity towards T2D risk in Arab-Emiratis compared to other ethnic groups. Sedentary time explains a bigger proportion of T2D risk compared to overall physical inactivity in Arab-Emiratis. I identified 40 novel loci in association with T2D (P-value < 5x10-6), with one loci reaching genome-wide significance mapping to MALRD1 (P-value = 1.6x10-8). Overall, results showed that previously reported T2D risk loci cannot fully account for the increased risk in Arab-Emiratis.
Conclusions
Increased T2D risk in Arab-Emiratis could be more attributable to central adiposity rather than BMI. Findings highlighted the negative impact of physical inactivity on insulin resistance and central adiposity in Arab-Emiratis, but its contribution towards their increased T2D risk is limited. Lastly, I identified 40 novel loci for T2D that potentially provide further insight into the genetic mechanisms underlying T2D in Arab-Emiratis.
Version
Open Access
Date Issued
2022-08
Date Awarded
2023-05
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Järvelin, Marjo-Riitta
Blakemore, Alexandra
Publisher Department
School of Public Health
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)