Contributions
Abstract: 113
Type: Educational Session
Abstract Category: N/A
Introduction: Heritable contributions to MS risk are undisputable. Analogous to other autoimmune diseases, individuals with MS tend to cluster in families. The recognition during the early 1970s of the influence of specific human leukocyte antigen (HLA) variants in MS susceptibility represented the first empirical demonstration linking disease risk with common genetic variation, but it was the polygenic model of MS heritability that provided the theoretical justification for assembling multicenter large DNA data sets to pursue GWAS.
Objectives: I will present a historical perspective on the progress made in MS genetics and discuss current work geared towards creating a more complete model that accurately represents the genetic landscape of MS susceptibility.
Aims: A contemporary model of MS pathogenesis needs to incorporate a deep understanding of the individual contributions of each common variant to the cellular phenotypes, and interactions with other genes and with the environment.
Methods: GWAS, linkage, targeted sequencing and functional gene studies will be discussed.
Results: More than 200 loci have been associated with MS susceptibility to date. There is extensive sharing of genetic risk variants between MS and other autoimmune diseases. This suggests a model in which a general risk for autoimmunity is inherited. Additional genetic (and epigenetic) determinants and environmental exposures are compounded to ultimately define the target organ of the autodestructive process.
Conclusion: The genetic architecture of MS has been largely unraveled by international, collaborative efforts. The next frontier appears to be the identification of their functional consequence, the pathways affected by these variants, and finally, the integration of multimodal data sources into a subject's medical record, a process that could bring the promise of precision medicine in MS one step closer.
Disclosure: Nothing to disclose
Abstract: 113
Type: Educational Session
Abstract Category: N/A
Introduction: Heritable contributions to MS risk are undisputable. Analogous to other autoimmune diseases, individuals with MS tend to cluster in families. The recognition during the early 1970s of the influence of specific human leukocyte antigen (HLA) variants in MS susceptibility represented the first empirical demonstration linking disease risk with common genetic variation, but it was the polygenic model of MS heritability that provided the theoretical justification for assembling multicenter large DNA data sets to pursue GWAS.
Objectives: I will present a historical perspective on the progress made in MS genetics and discuss current work geared towards creating a more complete model that accurately represents the genetic landscape of MS susceptibility.
Aims: A contemporary model of MS pathogenesis needs to incorporate a deep understanding of the individual contributions of each common variant to the cellular phenotypes, and interactions with other genes and with the environment.
Methods: GWAS, linkage, targeted sequencing and functional gene studies will be discussed.
Results: More than 200 loci have been associated with MS susceptibility to date. There is extensive sharing of genetic risk variants between MS and other autoimmune diseases. This suggests a model in which a general risk for autoimmunity is inherited. Additional genetic (and epigenetic) determinants and environmental exposures are compounded to ultimately define the target organ of the autodestructive process.
Conclusion: The genetic architecture of MS has been largely unraveled by international, collaborative efforts. The next frontier appears to be the identification of their functional consequence, the pathways affected by these variants, and finally, the integration of multimodal data sources into a subject's medical record, a process that could bring the promise of precision medicine in MS one step closer.
Disclosure: Nothing to disclose