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    You are here : Home » MS Research News » Familial Risk of Multiple Sclerosis Research

    Familial Risk of Multiple Sclerosis Research

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    Congenital abnormalities and Multiple Sclerosis

    MS & GeneticsAbstract (provisional)

    Background
    There is a strong maternal parent-of-origin effect in determining susceptibility to multiple sclerosis (MS). One hypothesis is that an abnormal intrauterine milieu leading to impaired fetal development could plausibly also result in increased susceptibility to MS. A possible marker for this intrauterine insult is the presence of a non-fatal congenital anomaly.

    Methods
    We investigated whether or not congenital anomalies are associated with MS in a population-based cohort. We identified 7063 MS index cases and 2655 spousal controls with congenital anomaly information from the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS).

    Results
    The frequency of congential anomalies were compared between index cases and controls. No significant differences were found.

    Conclusions
    Congenital anomalies thus do not appear to be associated with MS. However, we did not have complete data on types and severity of congenital anomalies or on maternal birth history and thus this study should be regarded as preliminary.

    Source: BMC Neurology © 1999-2010 BioMed Central Ltd (17/11/10)

    Disease onset in familial and sporadic primary progressive multiple sclerosis
    MS DiagnosisThe pathophysiology of primary progressive (PP) multiple sclerosis (MS) involves diffuse axonal degeneration which is believed to start early in the disease process, even before the onset of clinical symptoms.

    Symptomatic onset then occurs when this process reaches a threshold after which the axonal loss can no longer be compensated.

    A preliminary study showed that patients with familial PPMS had an earlier clinical onset than patients with sporadic disease, suggesting a hereditary component to the disease process of PPMS.

    In this study, we combined data from two large, population-based, longitudinal MS databases to investigate disease onset in familial and sporadic PPMS. We examined 411 patients with PPMS.

    There were no differences in gender distribution or onset symptoms between familial and sporadic PPMS. Patients with familial PPMS were significantly younger at disease onset (n = 84, median age: 37.6 years) than patients with sporadic disease (n = 327, median age: 42.7, p = 0.007). This difference was due to a greater proportion of familial cases with a disease onset before the age of 30 and a smaller proportion with disease onset between 40 and 50 years of age (p = 0.002).

    Gender had no significant effect on the age at disease onset.

    Further analyses showed that these findings were unlikely to be due to ascertainment bias towards an earlier diagnosis in familial cases.

    Our findings suggest a hereditary component to the disease process of PPMS. It would be worthwhile to identify patients with familial PPMS for future research on disease modifying genes in MS.

    Koch M, Zhao Y, Yee I, Guimond C, Kingwell E, Rieckmann P, Sadovnick D, Tremlett H.

    Faculty of Med., Div. of Neurology, Uni. of British Columbia, Vancouver, Canada/Dept. of Neurology; Uni. of Groningen; Groningen, The Netherlands.

    Source: Pubmed PMID: 20378663 (26/04/10)

    Age of Earliest MS Symptoms Inherited from Parents

    MS Brain

    Age of onset but not severity of Multiple Sclerosis inherited from parents.

    When more than one member of a family is affected by multiple sclerosis (MS), their ages at disease onset are likely to be similar, but disease severity may not be. These new findings have important implications for counselling patients, according to a study published in an issue of Neurology®, the scientific journal of the American Academy of Neurology.

    "We’ve known for some time that family influence plays a role in whether you are susceptible to MS, but it has not been clear whether your family influence affects the course of the disease," according to lead study author Alastair Compston, PhD, of the University of Cambridge Clinical School in Cambridge, United Kingdom.

    To address the question of family influence on the course of the disease, researchers examined data on 2,310 individuals from over 1,000 families in which at least two members had MS.

    They examined age at onset, disability, disease severity, and other features of the disease.

    The researchers found that age at onset of the disease was similar among family members, whether comparing parents to children or siblings with each other. They also found that siblings tended to have the same pattern of disease progression, while there was no correlation between the pattern in parents and children.

    The study also showed there was no correlation between the severity of the disease in one family member and severity in another member, whether siblings or parent and child. "Disease progression is often considered the indicator of severity," said Compston. "But, we found no evidence that disease severity is more likely to be similar between two family members with MS than two unrelated people with MS."

    The causes of the similarities in onset and progression pattern are largely unknown, as are the causes of MS itself. It is possible that genetic factors are responsible, but environmental factors shared by family members may also play a role.

    Compston says the study’s findings have significant implications for counselling patients. "People should not draw personal conclusions for their own MS prognosis and expected disease severity from observing the condition of their relatives with MS," he said.

    Source: Neurology (28/10)

    MS That Runs in Families May Be Worse
    Brain Damage From Multiple Sclerosis May Be More Severe in Patients With Family History of MS.

    Multiple sclerosis may cause more severe brain damage in patients who have a relative who had multiple sclerosis.

    Researchers reported that news today in Prague, Czech Republic, at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis.

    The scientists -- who work at the State University of New York at Buffalo -- included Robert Zivadinov, MD, PhD.

    They studied 759 MS patients, 26% of whom had a relative with multiple sclerosis. The patients got brain scans using magnetic resonance imaging (MRI).

    Zivadinov and colleagues analyzed the patients' brain scans. The scientists noticed more severe brain damage in the brain scans of patients with a family history of MS, compared with those with no relatives with MS.

    That pattern was stronger for MS patients with a parent or sibling who had MS, compared with patients who had a more distant relative with MS.

    However, family history of multiple sclerosis wasn't linked to the degree of disability due to MS, the length of time the patients had had MS, or how their MS had progressed.

    "This warrants further investigation," writes Zivadinov and colleagues.

    Source: 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Prague, Czech Republic, Oct. 11-14, 2007. News release, State University of New York at Buffalo. (15/10/07)

    Men, women equally pass on genetic risk of MS
    Men and women with multiple sclerosis equally transmit the genetic risk of the disease to their children, concludes a Canadian study published in Neurology, the medical journal of the American Academy of Neurology.

    The research contradicts results of a recent study that found fathers were more likely than mothers to transmit the risk of developing MS to their children.

    Researchers studied 3,088 Canadian families with one parent affected with MS.

    Of the 8,401 children in those families, 798 had MS. The study found equal transmission of the genetic risk of MS to children, with 9.41 per cent of fathers transmitting MS to their children compared to 9.76 per cent of mothers.

    "We also found there were equal numbers of daughters and sons receiving the genetic risk of the disease from their parents," said study author Dr. George Ebers from the University of Oxford.

    "Intriguingly, we also found when half-siblings both have MS, there is a clear maternal effect, with mothers much more likely to be the common parent."

    Ebers says the findings show no evidence of "the Carter effect," which was recently cited in a study that found men with MS were twice as likely to pass the risk of disease on to their children. According to the Carter effect, men are more resistant to MS because they carry a higher genetic load and thus are more likely to transmit the genetic risk of the disease to their children.

    "Our study involved 16 times as many people as the previous published study. It casts further doubt on the widely believed multiple gene mode of inheritance of susceptibility to MS," said Ebers.

    Canada has among the highest rates of multiple sclerosis in the world, as do many nations in northern Europe. That has prompted speculation genetics and geography may increase the risk for people who live in countries far from the equator.

    A study last year by Dr. Ebers found that women with multiple sclerosis now outnumber men in Canada by a ratio of more than three to one. They also found that this gender ratio has been rising for at least 50 years.

    Source: CTV.ca © CTV Globe Media 2007 All Rights Reserved.(28/06/07)

    Family Members With Multiple Sclerosis Likely To Share Onset Age, But Not Disease Severity
    When more than one member of a family is affected by multiple sclerosis (MS), their ages at disease onset are likely to be similar, but disease severity may not be. These new findings have important implications for counseling patients, according to a study published in the January 30, 2007, issue of Neurology®, the scientific journal of the American Academy of Neurology.

    "We've known for some time that family influence plays a role in whether you are susceptible to MS, but it has not been clear whether your family influence affects the course of the disease," according to lead study author Alastair Compston, PhD, of the University of Cambridge Clinical School in Cambridge, United Kingdom.

    To address the question of family influence on the course of the disease, researchers examined data on 2,310 individuals from over 1,000 families in which at least two members had MS. They examined age at onset, disability, disease severity, and other features of the disease.

    The researchers found that age at onset of the disease was similar among family members, whether comparing parents to children or siblings with each other. They also found that siblings tended to have the same pattern of disease progression, while there was no correlation between the pattern in parents and children.

    The study also showed there was no correlation between the severity of the disease in one family member and severity in another member, whether siblings or parent and child. "Disease progression is often considered the indicator of severity," said Compston. "But, we found no evidence that disease severity is more likely to be similar between two family members with MS than two unrelated people with MS."

    The causes of the similarities in onset and progression pattern are largely unknown, as are the causes of MS itself. It is possible that genetic factors are responsible, but environmental factors shared by family members may also play a role.

    Compston says the study's findings have significant implications for counseling patients. "People should not draw personal conclusions for their own MS prognosis and expected disease severity from observing the condition of their relatives with MS," he said.

    Note: This story has been adapted from a news release issued by American Academy of Neurology.

    Source: Sciencedaily Copyright © 1995-2007 ScienceDaily LLC (31/01/07)

    Familial effects on the clinical course of multiple sclerosis

    Background:
    Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease.

    Method:
    We evaluated 1,083 families with 2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent-child pairs.

    Results:
    There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent-child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings (correlation coefficient 0.18; p < 0.001) but not the parent-child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children (kappa –0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups (correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent-child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent–child pairs and no evidence for anticipation or effects of genetic loading.

    Conclusion:
    Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.

    This work follows from the individual GAMES screens that were supported by the Wellcome Trust (grant 057097). The Nordic study was supported by the EU Commission (project number BMH4-CT97-2422), B.D. is supported by the University Research Council (University of Leuven, Belgium), and F.Z. is supported by grants from the Bundesministerium für Bildung und Forschung, Germany.

    Disclosure: The authors report no conflicts of interest.

    Received February 20, 2006. Accepted in final form October 12, 2006.

    A. E. Hensiek, MD, PhD, S. R. Seaman, PhD, L. F. Barcellos, PhD, A. Oturai, MD, PhD, M. Eraksoi, MD, E. Cocco, PhD, L. Vecsei, MD, G. Stewart, PhD, B. Dubois, MD, PhD, J. Bellman-Strobl, MD, M. Leone, MD, O. Andersen, MD, K. Bencsik, MD, D. Booth, MD, PhD, E. G. Celius, MD, PhD, H. F. Harbo, MD, PhD, S. L. Hauser, PhD, R. Heard, MD, J. Hillert, MD, PhD, K. -M. Myhr, M. G. Marrosu, PhD, J. R. Oksenberg, PhD, C. Rajda, MD, S. J. Sawcer, MD, PhD, P. S. Sørensen, PhD, F. Zipp, MD and D.A.S. Compston, MD, PhD.

    From the Department of Clinical Neurosciences (A.E.H., S.J.S., D.A.S.C.), University of Cambridge Clinical School, UK; MRC Biostatistics Unit (S.R.S.), Institute of Public Health, University Forvie Site, Cambridge, UK; School of Public Health (L.F.B.), University of California, Berkley; Danish Multiple Sclerosis Research Centre (A.O., P.S.S.), Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark; University of Istanbul (M.E.), Turkey; Centro Sclerosi Multipla (E.C., M.G.M.), University of Caglieri, Sardinia, Italy; University of Szeged (L.V., K.B., C.R.), Albert Szent-Gyorgyi Medical and Pharmaceutical Center, Department of Neurology; Westmead Millennium Institute (G.S., D.B., R.H.), Sydney, Australia; University of Leuven (B.D.), Belgium; Institut fuer Neuroimmunologie (J.B.-S., F.Z.), Universitaetsklinikum Charite, Berlin, Germany; Clinica Neurologica (M.L.), Ospedale Maggiore della Carità, Novara, Italy; Department of Neurology (E.G.C., H.F.H.), Ullevål University Hospital, Oslo, Norway; Department of Neurology (L.F.B., S.L.H., J.R.O.), University of California at San Francisco; Department of Neurology (J.H.), Karolinska University Hospital-Huddinge, Karolinska Institute, Sweden; The Multiple Sclerosis National Competence Centre (K.-M.M.), Department of Neurology, Haukeland University Hospital and Department of Clinical Medicine Section for Neurology, University of Bergen, Norway; and Department of Neurology (O.A.), Göteborg University Hospital, Sweden.

    Address correspondence and reprint requests to Professor Alastair Compston, Department of Clinical Neuroscience, University of Cambridge Clinical School, Addenbrooke's Hospital, Box 165, Cambridge CB2 2QQ, UK; e-mail: [email protected]   

    Source: NEUROLOGY 2007;68:376-383 © 2007 American Academy of Neurology (30/01/07)

    Men with multiple sclerosis pass disease to offspring more often than women
    According to a new study, men transmit multiple sclerosis (MS) to their children 2.2 times more often than women in families where the father or mother and a child have multiple sclerosis.

    This study involved an investigation of 444 children of an MS-affected father or mother from 3,598 individuals in 206 families to compare the transmission of MS between affected men and women. The findings by researchers from Mayo Clinic, the University of California at San Francisco, the University of California at Berkeley and Kaiser Permanente will be published in the July 25 issue of the journal Neurology.

    "Fathers with MS tend to have more children who develop MS than do mothers with the disease," says Brian Weinshenker, M.D., Mayo Clinic neurologist and study investigator. "When we looked at a large population of MS patients, when there was a parent and a child who had MS in a family, the child with MS got the disease twice as often from the father rather than the mother."

    MS affects approximately 1 in 1,000 people, and it is twice as common in women as in men. In 85 percent of cases, no cause is known. For 15 percent of MS patients, a family member within a generation also is affected by the disease. For familial cases, no single gene has been identified that strongly predisposes a person to MS.

    "Rather, a combination of genes and unknown environmental factors work together to cause multiple sclerosis," says Orhun Kantarci, M.D., Mayo Clinic neurologist and lead author of the paper.

    The researchers theorise that men may have a greater "genetic load" of MS genes, which may explain their findings.

    "The hypothesis of the study is that men are more resistant to MS, so they need stronger or a larger number of genes in order to develop MS, and then pass these genes to their children," says Dr. Kantarci.

    He also explains that the overtransmission of MS by men in the study is not easily explained by hormonal differences between men and women or by genes on the sex chromosomes.

    The findings shouldn't change how men with MS are counseled about the risk to their offspring, say the researchers. The risk of having MS if a person has an affected parent is increased by about 20-fold compared to not having an affected parent; the additional risk by virtue of having an affected father is not sufficient to change patient counseling practices, says Dr. Kantarci.

    "The overtransmission by men is primarily of interest to scientists studying the mechanisms of genetic transmission of MS susceptibility," said Dr. Kantarci, "and may indicate that nontraditional, or so-called epigenetic factors, play some role in the transmission of MS."

    The investigators also indicate that their findings should be confirmed in another study by other researchers to be widely accepted.

    No intervention prevents men from passing on MS, say the researchers, who indicate the necessity for MS researchers to identify the reason for this overtransmission by men, including finding genes predisposing to the "parent-of-origin" effect observed in this study.

    Source: Mayo Clinic (25/07/06)

    Diabetes and MS linked in Danish study
    People with type 1 diabetes are more than three times more likely to develop multiple sclerosis (MS) than are those without diabetes, new research from Denmark shows.

    In addition, the two diseases appear to be linked, albeit to a weaker extent, within families.

    Both type 1 diabetes and MS are auto-immune diseases, in which the body mounts an aberrant immune response against its own tissues -- attacking insulin-producing cells in the case of diabetes, and the myelin sheath surrounding neurons in MS.

    The new, population-based study is not the first to reveal an association between type 1 diabetes and MS. However, previous evidence had come from relatively small numbers of patients.

    As reported in the Archives of Neurology, Dr. Nete M. Nielsen, from the Statens Serum Institut in Copenhagen, and colleagues assessed the occurrence of MS in 6078 patients with type 1 diabetes over more than a decade of follow-up.

    In addition, the researchers evaluated the presence of type 1 diabetes in 14,771 first-degree relatives of 11,862 MS patients.

    Eleven cases of MS developed in the diabetes patients, while only 3.38 cases would be expected based on the rates in the general population. Thus, patients with type 1 diabetes had a more than three-fold increased risk of MS.

    First-degree relatives of MS patients had a 63 percent increased risk of developing type 1 diabetes, the team calculated from their data. However, after accounting for the possibility of also being related to a patient with type 1 diabetes, the excess risk fell to 44 percent. "To our knowledge, the present study is the first truly nationwide cohort study to demonstrate intraindividual and, to a lesser degree, intrafamilial co-occurrence of MS and type 1 diabetes," the investigators write.

    "The underlying mechanisms remain unknown," they say, "but may involve both genetic and environmental factors."

    Source: Archives of Neurology, July 2006.

    Familial risk of multiple sclerosis: a nationwide cohort study

    Multiple sclerosis (MS) is known to accumulate within families. The magnitude of the familial risk, however, remains uncertain. Using a nationwide MS register and other national registers, the authors estimated relative and absolute risks of MS in a population-based cohort that included 19,615 first-degree relatives of 8,205 Danish MS patients followed from 1968 to 1997. The ratio of observed to expected numbers of MS cases served as the measure of the relative risk of MS. Lifetime risks of MS in first-degree relatives were estimated as the product of the relative risk and the national lifetime risk of MS.

    Overall, first-degree relatives had a sevenfold increased risk of MS (relative risk = 7.1, 95% confidence interval: 5.8, 8.8) (n = 90) compared with the background population. By modeling the individual incidence rate of MS as the sum of a familial component and a sporadic risk component, the familial excess lifetime risk was found to be 2.5% (95% confidence interval: 2.0, 3.2) among first-degree relatives of MS patients, irrespective of the gender of the proband and the relative. This percentage should be added to a sporadic absolute risk in the general population of 0.5% in women and 0.3% for men. Spouses of MS patients did not experience an increased risk of MS, suggesting no major role for environmental factors acting in adulthood.

    Nielsen NM, Westergaard T, Rostgaard K, Frisch M, Hjalgrim H, Wohlfahrt J, Koch-Henriksen N, Melbye M.

    Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen, Denmark.

    Source: Am J Epidemiol. 2005 Oct 15;162(8):774-8. Epub 2005 Aug 24.

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