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Locus for severity implicates CNS resilience in progression of multiple sclerosis, 2023, MS consortia

Discussion in 'Other health news and research' started by Jacob Richter, Jun 29, 2023.

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  1. Jacob Richter

    Jacob Richter Established Member (Voting Rights)

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    Post copied from the DecodeME thread:

    I agree the 85% response rate is fantastic - unheard of really. Decode ME is such a brilliant study.

    On a related note, I found the following UCSF and University of Cambridge study on MS, published yesterday, interesting:

    Scientists identify first genetic marker for MS severity | University of Cambridge

    "A study of more than 22,000 people with multiple sclerosis has discovered the first genetic variant associated with faster disease progression, which can rob patients of their mobility and independence over time [...] This gives us a new opportunity to develop new drugs that may help preserve the health of all who suffer from MS.”

    Are there lines of communication open between the Decode ME team and researchers collecting DNA sample sets to search for for susceptibility genes and causal mechanisms for diseases like MS? Hopefully there will opportunities over the long term to share lessons etc


    Edit: Published paper abstract added:
    https://www.nature.com/articles/s41586-023-06250-xLocus for severity implicates CNS resilience in progression of multiple sclerosis
    Abstract

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults1,2. Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases.

    We identified a significant association with rs10191329 in the DYSF–ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3–PIGC locus and significant heritability enrichment in CNS tissues.

    Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility3, these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS.
     
    Last edited by a moderator: Jun 29, 2023
    Jacob Richter, Jun 29, 2023
    #1
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  2. Hutan

    Hutan Moderator Staff Member

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    From @Jacob Richter's link on MS genes:
    Interesting, and it really underlines how important it is to set up patient registries that track patients over the course of their illness.

    @Andy or @Chris Ponting, if you have a spare moment, perhaps you could remind us what might happen after the initial DecodeME project? I guess you'd need a whole lot more funding to create an ongoing very large patient registry?

    Hopefully it won't take 50 years for the genetics of ME/CFS to be unravelled.
     
    Last edited by a moderator: Jun 29, 2023
    Hutan, Jun 29, 2023
    #2
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  3. ME/CFS Skeptic

    ME/CFS Skeptic Senior Member (Voting Rights)

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    Last edited by a moderator: Jun 29, 2023
    ME/CFS Skeptic, Jun 29, 2023
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  4. Chris Ponting

    Chris Ponting Established Member (Voting Rights)

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    Variant rs10191329 (minor allele frequency 17%) near to genes DYSF and ZNF638: p = 9.7x10-9 (whereas the usual significance threshold is p<5x10-8). This was then replicated (p=3.6x10-9). Effect size = 0.89 (0.015 standard error). Probably acts on dysferlin (DYSF) but could [also] be on ZNF638. No effect of Vitamin D on MS severity.
     
    Chris Ponting, Jun 29, 2023
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    MeSci, Jacob Richter, Michelle and 9 others like this.
  5. duncan

    duncan Senior Member (Voting Rights)

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    Seems more prudent to focus on determining the cause(s) of any disease or syndrome, rather than some purported innate deficiency that may or may not be responsible for the disease presenting faster or worse in a portion of the patient population.
     
    duncan, Jun 29, 2023
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  6. Mij

    Mij Senior Member (Voting Rights)

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    Genetic Variant Linked to Faster Progression of Multiple Sclerosis Found

    Source: Yale

    A study of more than 22,000 people with multiple sclerosis (MS) has for the first time identified a genetic variant associated with faster progression of the disease, an accumulation of disability that can rob patients of their mobility and independence over time.

    Summary: A new study involving over 22,000 people with Multiple Sclerosis (MS) has identified a genetic variant associated with the disease’s faster progression.

    The research discovered a genetic variant that significantly affects disease severity. This development brings us closer to understanding and combatting the progressive form of MS. The identified genetic variant accelerates disability, undermining patient mobility and independence over time.

    Key Facts:
    1. This is the first study that identifies a genetic variant that significantly increases the severity of MS.
    2. The variant is located between two genes, DYSF and ZNF638, which have no prior connection to MS, hinting at a possible mechanism for faster progression.
    3. MS patients inheriting this genetic variant from both parents see the time to needing a walking aid accelerated by nearly four years.
    https://neurosciencenews.com/genetics-progressive-ms-23546/
     
    Last edited by a moderator: Jun 29, 2023
    Mij, Jun 29, 2023
    #6
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  7. Hutan

    Hutan Moderator Staff Member

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    Regarding the funding:
    I wondered about whether there was a US government funded ME patient registry.

    There's this one:
    The Multiple Sclerosis Surveillance Registry: A Novel Interactive Database Within the Veterans Health Administration, 2020

    Objective
    To demonstrate the infrastructure and utility of an interactive health system database for multiple sclerosis (MS), we present the MS Surveillance Registry (MSSR) within the US Department of Veterans Affairs (VA).

    Background
    Disease specific databases can be helpful in the management of neurologic conditions but few are fully integrated into the electronic health record and linked to health system data. Creating a consistent information technology (IT) architecture and with ongoing support within disease specific registries has been a challenge.

    Methods
    Building the MSSR was initiated by an iterative process with an IT team and MS health care providers. A common registry platform shared by other VA disease specific registries (eg, traumatic brain injury and cancer) was used to develop the IT infrastructure. MS cases were entered online into the MS Assessment Tool at selected MS Centers of Excellence (MSCoE) clinics in the US. Other large VA databases linked to MSSR are reviewed. Patient demographic and clinical characteristics were compared and contrasted with the broader VA population and other US registry populations.

    Results
    We have enrolled 1,743 patients with MS in the MSSR through fiscal year 2019 from selected MS regional programs in the VA MSCoE network. The mean age of patients was 56.0 years, with a 2.7 male:female ratio. Among those with definite MS, the mean European Database for MS Disability Score was 4.7 and 75% had ever used an MS disease modifying therapy. A summary electronic dashboard was developed for health care providers to easily access demographic and clinical data for individuals and groups of patients. Data on comorbid conditions, pharmacy and prosthetics utilization, outpatient clinic visits, and inpatient admission were documented for each patient.

    Conclusions
    The MSSR is a unique electronic database that has enhanced clinical management of MS and serves as a national source for clinical outcomes.


    It could be worth pushing NIH to have a similar ME/CFS database established, perhaps within the Veterans Health Administration. I'm not sure what patient registry facility they have for Gulf War Illness.

    (minor edit)
     
    Last edited: Jun 29, 2023
    Hutan, Jun 29, 2023
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