The Genetic Predisposition of Paralytic Poliomyelitis Using Genome-Wide Association Studies

Abstract

Poliomyelitis is a foremost cause of paralysis among preventable diseases among children and adolescents globally. It is caused by persistent infection with poliovirus (PV). The PV infection does not always cause paralysis. A lack of immunization always increases the risk of paralytic polio. Genetic factors also been shown to affect the risk of developing the disease. The aim of this thesis is to investigate whether there are any genetic associations to paralytic poliomyelitis. This is based on a model for understanding its nature as a complex disease, where many genes are involved in contributing to the disease state. This is a population-based case-control study to identify genetic loci that influence disease risk. The study examined the association of genetic variation in single nucleotide polymorphisms (SNPs) across the genome with paralytic poliomyelitis susceptibility in the United States and Canadian survivors of poliomyelitis population, using a genome-wide association study (GWAS) approach. No association was observed. Loci that have been previously implicated were not found to affect the susceptibility to poliomyelitis in this study. The thesis consists of four chapters. Chapter 1 describes the epidemiology, pathogenesis and management of poliomyelitis. Chapter 2 gives an overview of the genomics of infectious diseases in general. Chapter 3 introduces the study population and presents the genome-wide analysis and associations with logistic regression to identify loci explore genes that might be associated with paralytic poliomyelitis and presents results. Chapter 4 discusses the implications of the results and explains future directions.