Asthma is a complex airway disease with many factors contributing to its development, resulting in several sub-phenotypes that have different underlying mechanisms. Obesity is a risk factor for asthma and its contribution to the risk of developing asthma was investigated in this project. The primary aim of this project was to identify possible sub-clusters of asthma-related genetic variants when considering obesity as risk factor for the disease. The secondary aim was to identify the causal pathways mediating the increased risk of asthma in each cluster. Genome-wide association studies (GWAS) summary statistics for body mass index (BMI) and asthma, were harmonized into one file, yielding a number of 91 variants after meeting criteria. Mendelian Randomisation Clustering was used to cluster genetic variants with similar causal estimates by which BMI influences asthma. Only one cluster was observed, suggesting that the genetic variants possibly act through the same causal pathway. The result also showed a small positive association between the genetic variants and asthma through BMI. This result is consistent with the calculated causal estimate, giving an odds ratio of 1.22, suggesting that obesity is associated with a higher risk of asthma. Possible molecular pathways were studied by first test for association between polygenic risk scores for BMI and around 3000 proteins available in the UK Biobank. The proteins that had a significant association were tested for association with asthma. The result show that some proteins are found to be associated with either increased or decreased asthma risk. These proteins are, however, not significant when corrected for multiple testing. The proteins' function and potential association with asthma were investigated, revealing that the GSTA1 protein may have a protective effect against asthma. These results are, however, difficult to interpret since they do not agree with results obtained in previous studies. More studies are required to investigate possible molecular pathways.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-533344 |
| Date | January 2024 |
| Creators | Ring, Elin |
| Publisher | Uppsala universitet, Genomik och neurobiologi |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Student thesis, info:eu-repo/semantics/bachelorThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | UPTEC X ; 24043 |
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