![]() Additionally, genetic decision rules that can be translated to aid existing clinical and environmental prognostic models in identifying MS subjects prone to future worsening of disability is not yet available. Although the International MS Genetic Consortium ( ) 39 have identified \(\sim\) 232 genetic loci to be associated with MS risk, limited studies have been conducted to identify those that predict future worsening of disability 25, 40, 41, 42, 43. Nevertheless, the genetic determinants of disability progression in MS remain elusive. There is, however, a plausible effect of genetic variants on MS progression, in particular relating to the severity of primary inflammation and/or relapses 37, 38. There have been notable proponents for no effect of currently known risk variants on MS outcomes after onset 24, 31, 32, 33, 34, 35, 36. However, despite these advances, the disease course remains largely unpredictable 26, with considerable inter- and intra-individual variability 27, 28, 29, 30. Particularly, older age, male sex, higher body mass index (BMI), higher number of previous relapses, exposure to higher latitudes, lower median income, higher depression scores, smoking status, higher baseline MRI T2 lesion load (T2L), cerebrospinal fluid (CSF) biomarkers, and neurofilament light chains (NFL), have been shown to predict the MS disease time-course to some degree 18, 19, 20, 21, 22, 23, 24, 25. Significant progress has been made towards elucidating the role of clinical and environmental factors that affects MS disability progression. Disease modifying therapies (DMTs) 7, 8, 9, 10 and vitamin D treatments (VitD) 11, 12, 13, 14, 15 are currently the only avenues used to prevent relapses, new brain and spinal cord lesions, and perhaps prevent worsening of neurological disability 16, 17. The focus has been to develop strategies and interventions to manage or slow disability progression, and to improve the quality of life of affected individuals. According to the World Atlas of MS (3rd edition), the number of people living with MS globally has increased from 2.3 million people in 2013 to 2.8 million people in 2020 5, 6. While the individual causes of MS are not known, the development of MS involves a complex interplay between genetic and environmental factors, particularly exposure to Epstein-Barr virus (EBV) 3, 4. MS occurs in people who have an underlying genetic susceptibility and are exposed to viral and environmental risk factors 2. ![]() ![]() Multiple sclerosis (MS) is a chronic neurodegenerative disease typified by the accumulation of disability at varying rates 1. The present study extends our knowledge of MS progression genetics and provides the basis of future studies regarding the functional significance of the identified loci. The derived ensembles produced a set of genetic decision rules that can be translated to provide additional prognostic values to existing clinical predictions, with the additional benefit of incorporating relevant genetic information into clinical decision making for PwMS. We examined associations of 208 previously established MS genetic loci with the risk of worsening of disability we learned ensemble genetic decision rules and validated the predictions in an external dataset. We aimed to identify MS genetic loci associated with worsening of disability over time, and to develop and validate ensemble genetic learning model(s) to identify people with MS (PwMS) at risk of future worsening. Limited studies have been conducted to identify and validate multiple sclerosis (MS) genetic loci associated with disability progression.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |