The identification of genetic markers of obesity risk in a South African black population

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, 2016Obesity 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.MT201

Assessing computational genomics skills: Our experience in the H3ABioNet African bioinformatics network

The H3ABioNet pan-African bioinformatics network, which is funded to support the Human Heredity and Health in Africa (H3Africa) program, has developed node-assessment exercises to gauge the ability of its participating research and service groups to analyze typical genome-wide datasets being generated by H3Africa research groups. We describe a framework for the assessment of computational genomics analysis skills, which includes standard operating procedures, training and test datasets, and a process for administering the exercise. We present the experiences of 3 research groups that have taken the exercise and the impact on their ability to manage complex projects. Finally, we discuss the reasons why many H3ABioNet nodes have declined so far to participate and potential strategies to encourage them to do so

Assessing computational genomics skills: Our experience in the H3ABioNet African bioinformatics network

The H3ABioNet pan-African bioinformatics network, which is funded to support the Human Heredity and Health in Africa (H3Africa) program, has developed node-assessment exer�cises to gauge the ability of its participating research and service groups to analyze typical genome-wide datasets being generated by H3Africa research groups. We describe a frame�work for the assessment of computational genomics analysis skills, which includes standard operating procedures, training and test datasets, and a process for administering the exer�cise. We present the experiences of 3 research groups that have taken the exercise and the impact on their ability to manage complex projects. Finally, we discuss the reasons why many H3ABioNet nodes have declined so far to participate and potential strategies to encourage them to do so

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes