Project 454419

Genetic variation is associated with susceptibility to infectious diseases and is also a likely key determinant of how well the immune system responds to vaccination. Since genetics can help design better treatments, understanding genetic determinants of immunity could help design better vaccines. However, there are two specific challenges with genetic determinant of vaccine response. First, most of our current knowledge is derived from European ancestry populations, but due to living in areas of high infectious diseases endemicity, non-European populations would likely benefit the most from vaccine genetic breakthroughs. Second, of particular interest to vaccine response is the human leukocyte antigen (HLA) system, a highly polymorphic segment of chromosome 6, which varies widely between different populations. The HLA requires dedicated analysis due to its complex architecture. Hence, there is a need for this research, especially in under-represented populations in large scale genetics research. In this program, we will measure the association between the genotype of 5150 individuals of diverse genetic ancestries and their vaccine responses. Study participants will come from 6 countries: Uganda, Burkina Faso, South Africa, Kenya, United Kingdom, and Bangladesh. This will ensure adequate genetic diversity for our analysis. We will perform genome-wide and HLA association studies on antibody response to diphtheria, tetanus, pertussis, hepatitis B, measles, pneumococcus, and polio vaccines. We will leverage our sample's genetic diversity to help shed light on the HLA by combining our results using random effect meta-analysis methods. Finally, we will follow-up on our results with modern bioinformatics methods to determine how best to translate our results to better treatment and vaccines for patients.