Abstract
Autoimmune diseases (AID) are the result of an imbalance in the immune response that leads to the destruction of cells and tissues. The understanding of these diseases through the perspective of human genetics has provided enormous insights due to the development of new technologies and new methods of analysis.
We describe a detailed analysis of the MHC-HLA locus, a region with a pivotal role in normal and pathogenic processes. With the use of new analytical methods, we demonstrate the independent association of new variants in regions outside those classically related to celiac disease (CeD) and additionally estimate a high genetic variance explained by the MHC-HLA region (~25%). This study demonstrates an outstanding challenge analyzing it.
We also analyzed the genetic associations in a population of South-Asian origin. With this analysis it was possible to demonstrate the importance of new large-scale analysis in non-European population in order to gain new insights into the biology of the complex traits.
We analyzed CeD together with of two related AID, type 1 diabetes (T1D) and rheumatoid arthritis (RA). In our analysis we found that double autoimmune (CeD+T1D) individuals posses more resemblance with the genetic factors predisposing to T1D, especially for the association in the MHC-HLA region. From the analysis of CeD and RA, it was interesting the identification of loci with a unique characteristic: even when the variants associated to CeD and RA were located in the same region, they were driving independent genetic effects and different biological downstream effects on gene expression.
We describe a detailed analysis of the MHC-HLA locus, a region with a pivotal role in normal and pathogenic processes. With the use of new analytical methods, we demonstrate the independent association of new variants in regions outside those classically related to celiac disease (CeD) and additionally estimate a high genetic variance explained by the MHC-HLA region (~25%). This study demonstrates an outstanding challenge analyzing it.
We also analyzed the genetic associations in a population of South-Asian origin. With this analysis it was possible to demonstrate the importance of new large-scale analysis in non-European population in order to gain new insights into the biology of the complex traits.
We analyzed CeD together with of two related AID, type 1 diabetes (T1D) and rheumatoid arthritis (RA). In our analysis we found that double autoimmune (CeD+T1D) individuals posses more resemblance with the genetic factors predisposing to T1D, especially for the association in the MHC-HLA region. From the analysis of CeD and RA, it was interesting the identification of loci with a unique characteristic: even when the variants associated to CeD and RA were located in the same region, they were driving independent genetic effects and different biological downstream effects on gene expression.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 2-Dec-2015 |
| Place of Publication | [Groningen] |
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| Print ISBNs | 978-90-367-8348-4 |
| Electronic ISBNs | 978-90-367-8349-1 |
| Publication status | Published - 2015 |