The role of genetic markers in obesity

Project title
Identification of genetic markers of obesity risk in a South African Black population

Research question
The overall aim of this study is to identify genetic markers of obesity risk and body composition in a South African Black population by genotyping Birth to Twenty cohort participants using the Illumina® Cardio-Metabochip and statistically testing genetic association. The association study will focus on loci associated with obesity measures in Europeans, to confirm if these loci are similarly associated with BMI variance and other body composition measures in Africans.

Rationale
Obesity is a considerable risk factor for cardiometabolic disease. Obesity is on the increase in developing countries such as South Africa, particularly in the South African Black population. A recent South African National Health and Nutrition Examination Survey (SANHANES-1) (Shisana et al., 2013) has shown that the prevalence of overweight and obesity was significantly higher in females than males (24.8% and 39.2% compared to 20.1% and 10.6% for females and males, respectively) in the South African population, with the highest figures for obesity being recorded in the South African black female population group. Obesity is a complex disease in that both genetic and environmental factors play a role, although the heritability of body mass index has been shown from studies to range between 40-70%, illustrating a strong genetic component. Most genome-wide-association-studies (GWAS) with regard to obesity and related anthropometric variables have been performed in European study cohorts with a paucity of African-embedded research. Therefore African populations in particular sub-Saharan African populations remain understudied.

As it is as yet unknown which genetic variants are associated with BMI variation or obesity risk in the South African black population, this project aims to address this question by analysing generated genotype information and available phenotype information. A long-term objective (not the current study) is that if we can identify genetic risk factors for obesity, perhaps we can screen for them in the general population, such that necessary interventions can be introduced to prevent or prolong the full-onset of the disease.

We are using the Illumina® Cardio-Metabochip as a tool to test whether associations with BMI and other body composition measures in European populations (data from GWAS), can be replicated in a South African Black population. The metabochip is a custom genotyping array containing 196,725 single nucleotide polymorphisms (SNP) markers that represent the top signals captured by GWAS for cardiometabolic and atherosclerotic traits (Voight, et al., 2012).

Research Output
1. Pillay, V., Crowther, N. J., Ramsay, M., Smith, G. D., Norris, S. A., & Lombard, Z. (2015). Exploring genetic markers of adult obesity risk in black adolescent South Africans—the Birth to Twenty Cohort. Nutrition & diabetes, 5(6), e157.
2. Wits Research Day Abstracts, published in South African Journal of Infectious Disease http://www.sajei.co.za/index.php/SAJEI/issue (Vol 30, No 2 (2015).

 

Supervisors
Dr. Zané Lombard; Ass. Prof. Nigel Crowther and Ass. Prof. Himla Soodyall