Identification of Shared and Distinct Gene-disease Associations Among Multiple Related Diseases and Multiple Subtypes of a Disease

• Author / Creator

  Franco-Villalobos, Conrado

• Genome-wide association study (GWAS) is an approach with high-throughput genotyping to uncover genetic susceptibilities of complex diseases. However, the genetic susceptibilities discovered usually carry very small risk increments. Additionally, the current approach to assess whether these genetic associations are shared among a group of diseases relies mainly on statistical significance alone, ignoring biologically relevant information such as magnitude and direction of the associations.

  The methodology proposed takes into account not only strength and direction of the associations but also the resemblance of the biological mechanism by using logic regression to generate a graphical representation of the similarity of the associations. We found evidence that 149 genetic associations have certain degree of uniqueness with Crohn's Disease, Rheumatoid Arthritis, and Type I Diabetes while 11 were shared between at least 2 diseases. Additionally, the gene-level analysis of TB cases stratified by age, strain, and lineage identified 3 new susceptibility genes (ZFHX1B, FER, and FAM77) associated with different TB subgroups.

• Subjects / Keywords

  • Loci
  • Crohn's Disease
  • Tuberculosis
  • Rheumatoid Arthritis
  • Logic Regression
  • GWAS
  • Type I Diabetes
  • SNP

• Graduation date

  Fall 2013

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R39C6S857

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.