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Post-GWAS Investigations for discovering pleiotropic gene effects in cardiovascular diseases

Abstract : Cardiovascular diseases (CVD) are complex diseases where many environmental and genetic factors are involved. Although the genetic aetiology of the CVD has been extensively investigated the last two decades, alternative approaches are needed in order to keep advancing in the pathophysiology of CVD. In this thesis, we propose an integrative approach to discover new genetic associations potentially involved in CVD. We chose previous GWAS hits and we centred our efforts in studying the pleiotropic and gene-gender interaction effects. Finally, we focused on the implementation of personalized genome-based therapy of the results obtained. New pleiotropic effects were discovered in the IL-6R and ABO genes relating them with different inflammatory and lipid phenotypes. In addition, we studied the gene-gender interaction effects, finding some sex-specific associations in two of the genes studied (ABO and GNB3). Further, we centered our efforts in implementing the results obtained during the thesis at the clinical level. One SNP within the TREM-1 gene was associated with increased levels of its protein and could be used as a predictor or risk biomarker for different diseases. Due to the high potential of this SNP, we applied a European patent and we are planning to start clinical trials in patients. Also, one haplotype in the IL-6R gene could be used in the treatment of personalized medicine. During this thesis, we discovered new gene-phenotype associations involved in CVD and other diseases. Our results help to better understand how the studied genes are exerting their effects at the molecular level. Our results will hopefully be taken into account in future personalized treatments
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Submitted on : Wednesday, September 5, 2018 - 3:09:19 PM
Last modification on : Tuesday, October 13, 2020 - 10:47:05 AM
Long-term archiving on: : Thursday, December 6, 2018 - 5:01:50 PM


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  • HAL Id : tel-01868508, version 1


Alex-Ander Aldasoro. Post-GWAS Investigations for discovering pleiotropic gene effects in cardiovascular diseases. Human health and pathology. Université de Lorraine, 2017. English. ⟨NNT : 2017LORR0247⟩. ⟨tel-01868508⟩



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