Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Progress in multiple sclerosis genetics.

ABSTRACT: A genetic component in the susceptibility to multiple sclerosis (MS) has long been known, and the first and major genetic risk factor, the HLA region, was identified in the 1970's. However, only with the advent of genome-wide association studies in the past five years did the list of risk factors for MS grow from 1 to over 50. In this review, we summarize the search for MS risk genes and the latest results. Comparison with data from other autoimmune and neurological diseases and from animal models indicates parallels and differences between diseases. We discuss how these translate into an improved understanding of disease mechanisms, and address current challenges such as genotype-phenotype correlations, functional mechanisms of risk variants and the missing heritability.

SUBMITTER: Goris A

PROVIDER: S-EPMC3492804 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Progress in multiple sclerosis genetics.

Goris An A Pauwels Ine I Dubois Bénédicte B

Current genomics 20121201 8

A genetic component in the susceptibility to multiple sclerosis (MS) has long been known, and the first and major genetic risk factor, the HLA region, was identified in the 1970's. However, only with the advent of genome-wide association studies in the past five years did the list of risk factors for MS grow from 1 to over 50. In this review, we summarize the search for MS risk genes and the latest results. Comparison with data from other autoimmune and neurological diseases and from animal mode ...[more]

PMID: 23730204

Similar Datasets

The genetics of multiple sclerosis in Latin America.

Project description:BACKGROUND:In today's globalised world, the heterogeneity of diseases such as multiple sclerosis has been studied since it has been suggested that ethnic differences, in conjunction with geographical and environmental factors, influence its incidence and prevalence. AIM:Based on this, an attempt has been made to identify the genetic factors that may confer risk or protection, not only for developing multiple sclerosis but also for determining the course of its evolution. RESULTS:In Latin America we have some data about this, which have been replicated in different populations in the entire region, with very different results compared with other regions, which could explain not only the different frequencies in some populations, such as Caucasians, but also the course of the disease and the response to actual treatments. However, in addition to these findings, other associated epigenetic mechanisms have also been found in our populations, such as levels of vitamin D, parasitic diseases, and indigenous populations. Therefore, the study of epigenetics plays a crucial role in understanding the physiopathology of multiple sclerosis. It must be studied in each population, especially in Latin America, due to its broad heterogeneity. CONCLUSION:It is very important to understand not only the genetic and external factors with these very specific effects in multiple sclerosis patients, but also the way they interact and are able to explain the frequency and some specific phenotypes of the disease in our populations besides the posibility to be a very specific treatment target.

| S-EPMC5617105 | biostudies-literature

Vitamin D and multiple sclerosis: epidemiology, immunology, and genetics.

Project description:This review provides a brief update of new research findings on the role of vitamin D in multiple sclerosis (MS).Evidence continues to accumulate supporting a protective role for vitamin D in MS risk and progression. Notable recent findings are that high 25-hydroxyvitamin D [25(OH)D] at the time of a first demyelinating event predicts a lower MS risk and a decreased risk of MS among offspring whose mothers had high predicted 25(OH)D levels. While a small vitamin D intervention study did not find an association between vitamin D and MS progression, this study had little statistical power, and larger trials will be needed to assess the therapeutic potential of vitamin D. Recent immunological studies also show modulation of the immune system by vitamin D that may be favorable for preventing or slowing the progression of MS. The demonstration that rare variants in CYP27B1, which encodes the enzyme that converts vitamin D to its active form, are strongly associated with MS risk supports a causal role of vitamin D deficiency as a risk factor for MS.Research on the nature of the association between vitamin D and MS risk and progression continues to progress; however, additional research on the timing and dose-response relationship will be crucial for designing future prevention and treatment trials.

| S-EPMC4815910 | biostudies-literature

Genetics of Multiple Sclerosis: An Overview and New Directions.

Project description:The contribution of genetic inheritance in multiple sclerosis was established early on. Although multiple sclerosis is not a Mendelian disease, its incidence and prevalence is higher in family members of affected individuals compared with the general population. Throughout the last decade, several small studies failed to identify any robust genetic associations besides the classic associations in the major histocompatibility complex region. During the past few years, genome-wide association studies (GWAS) have revolutionized the genetics of multiple sclerosis, uncovering more than 200 implicated genetic loci. Here, we describe these main findings and discuss the new avenues that these discoveries lay open.

| S-EPMC6027932 | biostudies-literature

The complex genetics of multiple sclerosis: pitfalls and prospects.

Project description:The genetics of complex disease is entering a new and exciting era. The exponentially growing knowledge and technological capabilities emerging from the human genome project have finally reached the point where relevant genes can be readily and affordably identified. As a result, the last 12 months has seen a virtual explosion in new knowledge with reports of unequivocal association to relevant genes appearing almost weekly. The impact of these new discoveries in Neuroscience is incalculable at this stage but potentially revolutionary. In this review, an attempt is made to illuminate some of the mysteries surrounding complex genetics. Although focused almost exclusively on multiple sclerosis all the points made are essentially generic and apply equally well, with relatively minor addendums, to any other complex trait, neurological or otherwise.

| S-EPMC2639203 | biostudies-literature

APOE epsilon4 and the cognitive genetics of multiple sclerosis.

Project description:BackgroundEvidence linking APOE to myelin repair, neuronal plasticity, and cerebral inflammatory processes suggests that it may be relevant in multiple sclerosis (MS). The purpose of this study was to determine whether the epsilon4 allele of APOE is associated with cognitive deficits in patients with MS.MethodUsing a case-control design, 50 patients with MS with the epsilon4 allele (epsilon4+) and 50 epsilon4-negative (epsilon4-) patients with MS were tested using a comprehensive battery of tests evaluating the cognitive domains most often affected in MS.ResultsThe epsilon4+ and epsilon4- patients with MS were well-matched with respect to demographic variables (age, gender, ethnicity, education, employment status, premorbid IQ) and disease variables (disease course, disease duration, Expanded Disability Status Scale, 25-foot timed walk, 9-hole pegboard test). In addition, the groups were similar in depressive symptoms, in the proportion of patients receiving disease-modifying therapy, and in carriage of the APOE epsilon2 allele. Results showed that none of the 11 cognitive outcome variables differed between epsilon4+ and epsilon4- patients with MS. Cognitive measures were also unrelated to epsilon4 interactions with age and gender. The incidence of overall cognitive dysfunction did not differ between epsilon4+ and epsilon4- groups, nor did failure on any test, and epsilon4 carriage was not a significant predictor of any adverse cognitive outcome. These negative results endured with the exclusion of epsilon2+ subjects from the analyses.ConclusionThis study does not support a role for the epsilon4 allele in cognitive dysfunction in multiple sclerosis.

| S-EPMC2875133 | biostudies-literature

Host Genetics and Gut Microbiome: Perspectives for Multiple Sclerosis.

Project description:As a complex disease, Multiple Sclerosis (MS)'s etiology is determined by both genetic and environmental factors. In the last decade, the gut microbiome has emerged as an important environmental factor, but its interaction with host genetics is still unknown. In this review, we focus on these dual aspects of MS pathogenesis: we describe the current knowledge on genetic factors related to MS, based on genome-wide association studies, and then illustrate the interactions between the immune system, gut microbiome and central nervous system in MS, summarizing the evidence available from Experimental Autoimmune Encephalomyelitis mouse models and studies in patients. Finally, as the understanding of influence of host genetics on the gut microbiome composition in MS is in its infancy, we explore this issue based on the evidence currently available from other autoimmune diseases that share with MS the interplay of genetic with environmental factors (Inflammatory Bowel Disease, Rheumatoid Arthritis and Systemic Lupus Erythematosus), and discuss avenues for future research.

| S-EPMC8394267 | biostudies-literature

Recent advances and future challenges in the genetics of multiple sclerosis.

Project description:Multiple sclerosis (MS) is the most common auto-inflammatory disease of the central nervous system, affecting more than 2 million individuals worldwide. It is a genetically complex disease, in which a substantial part of a person's liability to develop MS is caused by a combination of multiple genetic and non-genetic (e.g., environmental) risk factors. Increasing this complexity, many of the involved risk factors likely interact in an intricate and hitherto ill-defined fashion. Despite these complexities, and owing greatly to the advent and application of large-scale genome-wide association studies, our understanding of the genetic factors underlying MS etiology has begun to gain unprecedented momentum. In this perspective, I will summarize some recent advances and outline future challenges in MS genetics research.

| S-EPMC4094909 | biostudies-other

What role for genetics in the prediction of multiple sclerosis?

Project description:For most of us, the foundations of our understanding of genetics were laid by considering Mendelian diseases in which familial recurrence risks are high, and mutant alleles are both necessary and sufficient. One consequence of this deterministic teaching is that our conceptualization of genetics tends to be dominated by the notion that the genetic aspects of disease are caused by rare alleles exerting large effects. Unfortunately, the preconceptions that flow from this training are frequently erroneous and misleading in the context of common traits, where familial recurrence risks are modest, and for the most part the relevant alleles are neither rare, necessary, nor sufficient. For these common traits, the genetic architecture is far more complex, with susceptibility rather than causality resulting from the combined effects of many alleles, each exerting only a modest effect on risk. None of these alleles is sufficient to cause disease on its own, and none is essential for the development of disease. Furthermore, most are carried by large sections of the population, the vast majority of which does not develop the disease. One consequence of our innate belief in the Mendelian paradigm is that we have an inherent expectation that knowledge about the genetic basis for a disease should allow genetic testing and thereby accurate risk prediction. There is an inevitable feeling that the same should be true in complex disease, but is it?

| S-EPMC2830384 | biostudies-literature

The genetics of multiple sclerosis: an up-to-date review.

Project description:Multiple sclerosis (MS) is a prevalent inflammatory disease of the central nervous system that often leads to disability in young adults. Treatment options are limited and often only partly effective. The disease is likely caused by a complex interaction between multiple genes and environmental factors, leading to inflammatory-mediated central nervous system deterioration. A series of genomic studies have confirmed a central role for the immune system in the development of MS, including genetic association studies that have now dramatically expanded the roster of MS susceptibility genes beyond the longstanding human leukocyte antigen (HLA) association in MS first identified nearly 40 years ago. Advances in technology together with novel models for collaboration across research groups have enabled the discovery of more than 50 non-HLA genetic risk factors associated with MS. However, with a large proportion of the disease heritability still unaccounted for, current studies are now geared towards identification of causal alleles, associated pathways, epigenetic mechanisms, and gene-environment interactions. This article reviews recent efforts in addressing the genetics of MS and the challenges posed by an ever increasing amount of analyzable data, which is spearheading development of novel statistical methods necessary to cope with such complexity.

| S-EPMC5967887 | biostudies-literature

Beyond the Magic Bullet: Current Progress of Therapeutic Vaccination in Multiple Sclerosis.

Project description:Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) characterized by neuroinflammation, neurodegeneration and impaired repair mechanisms that lead to neurological disability. The crux of MS is the patient's own immune cells attacking self-antigens in the CNS, namely the myelin sheath that protects nerve cells of the brain and spinal cord. Restoring antigen-specific tolerance via therapeutic vaccination is an innovative and exciting approach in MS therapy. Indeed, leveraging the body's attempt to prevent autoimmunity, i.e., tolerization, focuses on the underlying cause of the disease and could be the key to solving neuroinflammation. In this perspective, antigen-specific vaccination targets only the detrimental and aberrant immune response against the specific disease-associated antigen(s) involved while retaining the capacity of the immune system to respond to unrelated antigens. We review the experimental approaches of tolerance-inducing vaccination in relapsing and progressive forms of MS that have reached the clinical development phase, including vaccination with autologous T cells, autologous tolerogenic dendritic cells, T cell receptor peptide vaccination, altered peptide ligand, ATX-MS-1467, cluster of differentiation (CD)-206-targeted liposomal myelin basic protein peptides and DNA vaccination. Failures, successes and future directions are discussed.

| S-EPMC5976685 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data