| Summary: | A thesis
Submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of
the requirements for the degree of
Doctor of Philosophy
Johannesburg, South Africa
15 July, 2016 === Obesity is a common risk factor for non-communicable disease and is most often
described in relation to body mass index (BMI), although it is not the best predictor of body
composition. Heritability estimates of obesity (predominantly based on Europeans) suggest
that there is a significant genetic component. The latest genome-wide association study
(GWAS) of obesity-related traits have identified over hundred loci contributing to BMI alone.
These findings have yet to be robustly replicated in African populations.
The aim of this study was to assess whether risk loci previously associated with body
composition in European populations showed a similar trend in a South African black
population by:
i. Replicating the association of six SNPs previously linked to adult BMI, in an
adolescent cohort (the Birth to twenty cohort (Bt20); N=990).
ii. Performing a replication and fine-mapping study by genotyping participants within this
same cohort using the Metabochip (N=2273).
iii. Estimating the narrow-sense heritability (h2) of body composition measures in this
cohort.
In the candidate gene analysis, three of the SNPs tested were significantly associated
with BMI, and showed a consistent (albeit smaller) directional effect to that observed in non-
African cohorts.
Results from the replication and fine-mapping analyses reaffirmed that several loci
including SEC16B, NEGR1, FTO, TMEM18, WARS2, NRXN3, and SP110 previously found
to be associated with body composition, were similarly associated in this African cohort. The
associated loci were replications of previous findings but they do not involve the same SNPs
observed in European, African-American and Asian populations. This suggests that GWASidentified
variants of body composition are tagged by different SNPs in an African cohort. An
important finding of this study was the observation of ten cross-phenotype associations.
Heritability estimates for most of the body composition phenotypes were similar to
estimates derived for European populations, albeit trending towards the upper limits of such
heritability measures.
This study highlights the importance of assessing genetic factors for body
composition in urban black South Africans. Results from this study suggests that more indepth
genomic studies in larger cohorts will reveal novel SNP associations for body
composition and insight into the aetiology of obesity. === MT2017
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