On 10 May 2021, Anders Ulrik Eliasen will defend his PhD thesis: Analysis of epistasis in childhood asthma
Time: 13:00
Place: Zoom, register for the defence here:
https://dtudk.zoom.us/meeting/register/u5csdO2grDsiHtGxM89z0F5OTWs3LQsbMu1Q
Principal supervisor: Professor Anders Gorm Pedersen
Co-supervisor: Professor Klaus Bønnelykke
Co-supervisor: Professor Hans Bisgaard
Co-supervisor: Associate Professor Tarunveer Singh Ahluwalia
Co-supervisor: Associate Professor Morten Arendt Rasmussen
Examiners:
Associate Professor Elena Papaleo, DTU Health Tech
Dr. Marie Standl, Helmholtz Zentrum München
Professor Anders Albrechtsen, University of Copenhagen
Chairperson at defence:
Professor Morten Nielsen
Abstract:
The sequencing of the first human genome in 2000 created a new scientific field within genetics denounced genome-wide association studies. These studies examine how genetic variations in a population attribute to disease development. Through this method, thousands of genes have been found to increase individual predisposition towards disease. However, a limitation of genome-wide association studies is that they only consider the contribution of individual genes to disease risk. Studies in model organisms provide evidence that interactions between genes influence various traits. The concept of genetic interactions is known as epistasis. Similar interaction effects may be present in the human genome as well. Discovery of epistasis signals involved in human diseases will provide new information on disease pathobiology and the genome's function.
The thesis presents work within genome-wide association studies of childhood asthma. The aim was to examine the role of genetic interactions involved in childhood asthma disease development. Towards this aim, we conducted a large genome-wide association study of severe childhood asthma, revealing a novel gene associated with the disease, which showed evidence of interaction with an additional gene. Based on this finding, we hypothesized that other genetic interactions might also be associated with childhood asthma. Therefore, we developed a statistical model to search for genetic interactions, resulting in the discovery of an additional genetic interaction. These findings provide novel insight into the pathogenesis of childhood asthma. Furthermore, it is the first example of epistasis discovered for childhood asthma and among the few examples ever found for human disease.