@article{Characterizing:5712,
      recid = {5712},
      author = {Clay, Selene Marilyn},
      title = {Characterizing Genetic Risks for Asthma},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2023-03},
      pages = {153},
      abstract = {Asthma is a disease of the airways with significant  clinical heterogeneity regarding age-of-onset,  co-occurrence with allergic diseases, lung function  measures, and more. Genome-wide association studies (GWAS)  have successfully reported over 150 asthma susceptibility  loci. However, uncovering the causal genes and mechanisms  underlying its pathogenesis has been challenging in part  due to extensive linkage disequilibrium (LD), which makes  it difficult to uncover the specific causal variants and  genes, and in part because most asthma GWAS are often  conducted in populations of European ancestries with  limited information on asthma subtypes and associated  traits. In this thesis, I address these gaps through  complementary approaches that identify putatively genes in  two major subtypes of asthma and in asthma-associated  quantitative traits. First, I examined one of the most  highly associated asthma loci on chromosome 6p21, encoding  the human leukocyte antigen (HLA) genes in childhood-onset  asthma and adult-onset asthma. Using Bayesian approaches  for fine mapping both GWAS loci and gene expression in  three different asthma-relevant cell types, I identified  putatively causal childhood- and adult-onset asthma  variants that are both shared and distinct to each type of  asthma and highlight roles for both gene expression and  protein coding variation in the HLA genes for asthma risk.  In the second project I examine the contribution of rare  variants to specific asthma-associated quantitative  phenotypes in a population of children of diverse  ancestries. I examined whole genome sequencing data and  detailed clinical information reflecting the major  allergic, pulmonary, and immune components of asthma. I  performed gene-based variant set tests and followed up  associations with independent, predicted gene expression  and mouse knockout resources. Overall, I report novel  associations between genes and allergic and inflammatory  phenotypes. Together, these studies build on the results of  asthma GWASs, identifying novel variants and genes  associated with asthma and its associated phenotypes.},
      url = {http://knowledge.uchicago.edu/record/5712},
      doi = {https://doi.org/10.6082/uchicago.5712},
}