A thesis
submitted to the School of Molecular and Cell Biology, Faculty of Science, University
of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree
of
Doctor of Philosophy
June 2017
Johannesburg, South Africa / Non-communicable diseases (NCDs) pose an increasing burden on public health and economic
growth worldwide. The highest increase in prevalence and death rates of NCDs has been seen in low
and middle-income countries (LMICs). World Health Organization (WHO) estimates that by 2030,
NCDs will account for five times as many deaths as communicable diseases in LMICs and that there
will be more than 2.16 billion overweight and 1.12 billion obese individuals in the world. It is also
estimated that by 2020 NCDs will contribute 80 percent of the global burden of disease and the
largest increase in NCD deaths will occur in Africa. Recent reports indicate that six of the ten leading
natural causes of death in South Africa are NCDs.
There are few studies that have used longitudinal data to understand the effects of life-course
childhood adiposity on future health risks and the early life factors responsible for variations in lifecourse
childhood obesity. However, it is not known whether there is a genetic basis for the variability
in BMI developmental patterns over time. Lack of comprehensive longitudinal and genetic
association data for obesity have made it difficult to do such studies in an African setting. It is still not
clear whether the same genetic variants associated with obesity in Europeans and other populations
are also associated with these traits in African populations. Understanding the genetic contribution to
obesity in the black South African population may help to come up with effective interventions to
deal with this emerging epidemic in Africa.
The aim of this thesis was to better understand the contribution of genetics and explain the
longitudinal genetic basis of childhood and adolescence obesity in black South African children. To
deal with this, I firstly studied identification of distinct trajectories of BMI and then relate the
established BMI trajectories to the future health risks of elevated blood pressure. Secondly, I explored
the early life factors behind BMI trajectory membership, this would help to identify factors that may
accelerate an individual’s progression from a normal BMI trajectory pattern membership to the one
characterized with elevated BMI. Then lastly, I looked at the additive genetic effect for BMI and
determine whether genetic risk of obesity in early adulthood was mediated by early life rapid growth.
Results showed variation in BMI developmental patterns between boys and girls; three and four
distinct sex-specific BMI trajectories were identified in boys and girls respectively. Children
belonging to early onset overweight or obese BMI trajectories, characterized by elevated BMI, had an
increased risk of elevated blood pressure in late adolescence, compared to their peers in the normal
trajectories.
Rapid conditional relative weight gain in early life was associated with increased risk of belonging to
a BMI trajectory characterized by consistent elevated BMI over time. Individuals in overweight or
obese trajectories had a higher chance of being overweight or obese in early adulthood.
I found that a genetic risk score, based on known adult BMI Caucasian risk variants, showed
significant longitudinal effects of genetic loci with BMI in childhood and adolescent and significant
age-GRS interactions were observed. A higher genetic risk score predicted membership of early onset
obese or overweight BMI trajectories. The genetic risk of obesity at 18 years of age was mediated by
pre-adolescence and adolescence rapid weight gain.
The results from this thesis emphasize the importance of studying individual’s BMI developmental
patterns when studying development and progression of obesity. These findings also show that the
information obtained from GWAS done in other populations can be equally relevant to African
populations and this could be used in early identification of individuals at increased risk of obesity
and other NCDs risk factors. Combing genetic risk score, BMI trajectories membership and weight
status can be used to help improve the screening process of individuals to be targeted in coming up
with targeted educational and behavior intervention programmes for obesity. These programmes
should target individuals at risk at early stage in order to reduce the adverse health risk outcomes later
in life. / MT 2017
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/23491 |
| Date | January 2017 |
| Creators | Munthali, Richard Junganiko |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | Online resource (xvii, 165 leaves), application/pdf |
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