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Age of onset in concordant twins and other relative pairs with multiple sclerosis.

https://arctichealth.org/en/permalink/ahliterature150146
Source
Am J Epidemiol. 2009 Aug 1;170(3):289-96
Publication Type
Article
Date
Aug-1-2009
Author
A Dessa Sadovnick
Irene M Yee
Colleen Guimond
Jacques Reis
David A Dyment
George C Ebers
Author Affiliation
Department of Medical Genetics, Vancouver Coastal Health Authority-University of British Columbia Hospital, G-920 Detwiller Pavilion, Vancouver, British Columbia, Canada. sadovnik@infinet.net
Source
Am J Epidemiol. 2009 Aug 1;170(3):289-96
Date
Aug-1-2009
Language
English
Publication Type
Article
Keywords
Adult
Age of Onset
British Columbia - epidemiology
Diseases in Twins - diagnosis - epidemiology - genetics
Family
Female
Genetic Predisposition to Disease
Humans
Male
Multiple Sclerosis - diagnosis - epidemiology - genetics
Parents
Pedigree
Risk factors
Siblings
Time Factors
Twins - genetics
Twins, Dizygotic - genetics
Twins, Monozygotic - genetics
Abstract
The ages of onset in multiple sclerosis cases span more than 7 decades. Data are presented for affected relative pairs from a Canadian population base of 30,000 multiple sclerosis index cases (1993-2008). The effects of genetic sharing, parent of origin, intergenerational versus collinear differences, and gender on the ages of onset were evaluated in the following concordant pairs: monozygotic twins (n = 29), dizygotic twins (n = 10), siblings (n = 614), first cousins (n = 405), half siblings (n = 29), parent/child (n = 285), and aunt/uncle/niece/nephew (avunculars) (n = 289). Fisher's z test assessed intraclass correlation (r) for ages of onset. Correlations for monozygotic twins, dizygotic twins, full siblings, and first cousins were 0.60, 0.54, 0.20, and 0.10, respectively. Dizygotic twins resembled monozygotic twins more than siblings. The age-of-onset correlation for maternal half siblings (r = 0.37) was higher than that for paternal half siblings (r = 0.26), consistent with other observations suggesting an intrauterine environmental effect on multiple sclerosis risk. Intergenerational comparisons are complicated by substantial increases of multiple sclerosis incidence over time. Genetic loading (familial vs. sporadic cases) did not generally influence the age of onset, but correlation of age of onset in multiple sclerosis relative pairs was proportional to genetic sharing. A maternal parent-of-origin effect on the age of onset in collinear generations was suggested.
Notes
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PubMed ID
19546151 View in PubMed
Less detail

An extended genome scan in 442 Canadian multiple sclerosis-affected sibships: a report from the Canadian Collaborative Study Group.

https://arctichealth.org/en/permalink/ahliterature180707
Source
Hum Mol Genet. 2004 May 15;13(10):1005-15
Publication Type
Article
Date
May-15-2004
Author
David A Dyment
A Dessa Sadovnick
Cristen J Willer
Holly Armstrong
Zameel M Cader
Steven Wiltshire
Bernadette Kalman
Neil Risch
George C Ebers
Author Affiliation
The Wellcome Trust Center for Human Genetics, Oxford, UK.
Source
Hum Mol Genet. 2004 May 15;13(10):1005-15
Date
May-15-2004
Language
English
Publication Type
Article
Keywords
Canada - ethnology
Chromosomes, Human, Pair 6 - genetics
Gene Frequency
Genes, MHC Class II - genetics
Genetic markers
Genetic Testing
Genome, Human
Humans
Linkage Disequilibrium
Microsatellite Repeats - genetics
Multiple Sclerosis - genetics
Polymorphism, Single Nucleotide
Population - genetics
Siblings
Abstract
Multiple sclerosis (MS) is a complex trait with a sibling relative risk (lambda(sibs)) between 18 and 36. We report a multistage genome scan of 552 sibling pairs from 442 families, the largest MS family sample assessed for linkage. The first stage consisted of a genome scan for linkage with 498 microsatellite markers at an average spacing of 7 cM in 219 sibling pairs. The second stage involved further genotyping of markers from positive regions in an independent sample of 333 affected sibling pairs. The global distribution of allele sharing for all markers showed a shift towards greater sharing within the affected sibling pair group but not in the discordant sibling pair group. This shift indicates that the number of contributing genetic factors is likely to be moderate to large. Only markers at chromosome 6p showed significant evidence for linkage (MLOD=4.40), while other regions were only suggestive (1p, 2q, 5p, 9q, 11p, 12q, 18p, 18q and 21q) with MLODs greater than 1.0. The replication analysis involving all 552 affected sibling pairs confirmed suggestive evidence for five locations, namely, 2q27 (MLOD=2.27), 5p15 (MLOD=2.09), 18p11 (MLOD=1.68), 9q21 (MLOD=1.58) and 1p31 (MLOD=1.33). Suggestive linkage evidence for a previously reported location on chromosome 17q (MLOD=1.67) and a prior association with marker D17S789 was replicated. We showed that the overall excess allele sharing we observed for the entire sample was due to increased allele sharing within the DRB1*15 negative subgroup alone. This observation is most consistent with a model of genetic heterogeneity between HLA and other genetic loci. These findings offer guidance for future genetic studies including dense SNP linkage disequilibrium analysis.
PubMed ID
15069025 View in PubMed
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Association between microchimerism and multiple sclerosis in Canadian twins.

https://arctichealth.org/en/permalink/ahliterature168314
Source
J Neuroimmunol. 2006 Oct;179(1-2):145-51
Publication Type
Article
Date
Oct-2006
Author
Cristen J Willer
Blanca M Herrera
Katie M E Morrison
A D Sadovnick
George C Ebers
Author Affiliation
Department of Clinical Neurology, University of Oxford, Oxford, UK.
Source
J Neuroimmunol. 2006 Oct;179(1-2):145-51
Date
Oct-2006
Language
English
Publication Type
Article
Keywords
Canada
Chimerism
Diseases in Twins
Female
Humans
Male
Multiple Sclerosis - genetics
Pedigree
Polymerase Chain Reaction
Twins, Dizygotic - genetics
Twins, Monozygotic - genetics
Abstract
Microchimerism, the persistence of foreign cells thought to derive from previous pregnancies, has been associated with autoimmune diseases. A maternal parent-of-origin effect in MS remains unexplained. We tested for microchimerism in monozygotic and dizygotic twin-pairs with MS. Microchimerism was associated with MS in affected females from monozygotic concordant pairs when compared to both affected (p=0.020) and unaffected (p=0.025) females in monozygotic discordant pairs. Microchimerism was increased in affected females of dizygotic discordant pairs (p=0.059). The rate of microchimerism was significantly higher in affected twins than in unaffected co-twins (p=0.0059). These observations show an association in twins between the presence of microchimerism and having MS.
PubMed ID
16843535 View in PubMed
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Association of infectious mononucleosis with multiple sclerosis. A population-based study.

https://arctichealth.org/en/permalink/ahliterature152691
Source
Neuroepidemiology. 2009;32(4):257-62
Publication Type
Article
Date
2009
Author
Sreeram V Ramagopalan
William Valdar
David A Dyment
Gabriele C DeLuca
Irene M Yee
Gavin Giovannoni
George C Ebers
A Dessa Sadovnick
Author Affiliation
Wellcome Trust Centre for Human Genetics, Oxford, UK.
Source
Neuroepidemiology. 2009;32(4):257-62
Date
2009
Language
English
Publication Type
Article
Keywords
Canada - epidemiology
Case-Control Studies
Chickenpox - epidemiology - prevention & control
Chickenpox Vaccine - administration & dosage
Cohort Studies
Disease Susceptibility
Female
Hepatitis B vaccines - administration & dosage
Humans
Infectious Mononucleosis - epidemiology
Influenza Vaccines - administration & dosage
Male
Measles - epidemiology - prevention & control
Measles Vaccine - administration & dosage
Middle Aged
Multiple Sclerosis - epidemiology - etiology
Mumps - epidemiology - prevention & control
Mumps Vaccine - administration & dosage
Risk factors
Rubella - epidemiology - prevention & control
Rubella Vaccine - administration & dosage
Sex Factors
Abstract
Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Several studies have attempted to correlate exposure to viral illness with the subsequent development of MS. Here in a population-based Canadian cohort, we investigate the relationship between prior clinical infection or vaccination and the risk of MS.
Using the longitudinal Canadian database, 14,362 MS index cases and 7,671 spouse controls were asked about history of measles, mumps, rubella, varicella and infectious mononucleosis as well as details about vaccination with measles, mumps, rubella, hepatitis B and influenza vaccines. Comparisons were made between cases and spouse controls.
Spouse controls and stratification by sex appear to correct for ascertainment bias because with a single exception we found no significant differences between cases and controls for all viral exposures and vaccinations. However, 699 cases and 165 controls reported a history of infectious mononucleosis (p
PubMed ID
19209005 View in PubMed
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Association of smoking with risk of multiple sclerosis: a population-based study.

https://arctichealth.org/en/permalink/ahliterature115893
Source
J Neurol. 2013 Jul;260(7):1778-81
Publication Type
Article
Date
Jul-2013
Author
Sreeram V Ramagopalan
Joshua D Lee
Irene M Yee
Colleen Guimond
Anthony L Traboulsee
George C Ebers
A Dessa Sadovnick
Author Affiliation
Medical Research Council Functional Genomics Unit and Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Source
J Neurol. 2013 Jul;260(7):1778-81
Date
Jul-2013
Language
English
Publication Type
Article
Keywords
Adult
Canada
Disease Susceptibility
Female
Humans
Longitudinal Studies
Male
Middle Aged
Multiple Sclerosis - etiology
Odds Ratio
Pregnancy
Prenatal Exposure Delayed Effects
Questionnaires
Risk factors
Smoking - adverse effects
Tobacco Smoke Pollution - adverse effects
Abstract
Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Several studies have shown an association between smoking and MS risk. Here, in a population-based Canadian cohort, we investigate the relationship between personal and maternal smoking exposure and the risk of MS. Using the longitudinal Canadian database, 3,157 MS cases and 756 spouse controls were administered questionnaires on active and passive smoking history. Mothers of cases and controls were also asked about their smoking exposure during pregnancy. The MS cases were more likely to have smoked than spouse controls (odds ratio 1.32, 95 % confidence interval 1.10-1.60, p = 0.003). This association was driven by an excess of ever-smokers in male MS cases. No association was seen with maternal active or passive smoking exposure during pregnancy. Ever-smoking is associated with increased MS risk in males. Further work is needed to understand the mechanism underlying this association.
PubMed ID
23455932 View in PubMed
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Childhood cow's milk allergy and the risk of multiple sclerosis: a population based study.

https://arctichealth.org/en/permalink/ahliterature145899
Source
J Neurol Sci. 2010 Apr 15;291(1-2):86-8
Publication Type
Article
Date
Apr-15-2010
Author
Sreeram V Ramagopalan
David A Dyment
Colleen Guimond
Sarah-Michelle Orton
Irene M Yee
George C Ebers
A Dessa Sadovnick
Author Affiliation
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Source
J Neurol Sci. 2010 Apr 15;291(1-2):86-8
Date
Apr-15-2010
Language
English
Publication Type
Article
Keywords
Age of Onset
Canada
Case-Control Studies
Child
Child, Preschool
Cohort Studies
F Factor
Female
Humans
Logistic Models
Longitudinal Studies
Male
Milk Hypersensitivity - epidemiology
Multiple Sclerosis - epidemiology
Risk factors
Spouses
Abstract
Autoimmune mechanisms are thought to have a major role in the pathogenesis of multiple sclerosis (MS) and vitamin D is hypothesised to contribute to disease susceptibility. Cow's milk allergy (CMA) is a common childhood allergy arising from an immune system imbalance and can also lead to vitamin D deficiency due to dairy food avoidance. Here, we investigated whether or not CMA influences the subsequent risk to develop MS in a population-based cohort. We identified 6638 MS index cases and 2509 spousal controls with CMA information from the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). Frequency of CMA was compared between index cases and controls. No significant differences were found. Childhood CMA thus does not appear to be a risk factor for MS.
PubMed ID
20096420 View in PubMed
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Clustering of autoimmune disease in families at high risk for multiple sclerosis?

https://arctichealth.org/en/permalink/ahliterature165121
Source
Lancet Neurol. 2007 Mar;6(3):206-7; author reply 207
Publication Type
Article
Date
Mar-2007

Environmental factors and multiple sclerosis.

https://arctichealth.org/en/permalink/ahliterature158771
Source
Lancet Neurol. 2008 Mar;7(3):268-77
Publication Type
Article
Date
Mar-2008
Author
George C Ebers
Author Affiliation
University Department of Clinical Neurology, Level 3, West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK. george.ebers@clneuro.ox.ac.uk
Source
Lancet Neurol. 2008 Mar;7(3):268-77
Date
Mar-2008
Language
English
Publication Type
Article
Keywords
Canada - epidemiology
Disease Susceptibility - epidemiology
Environment
Humans
Incidence
Multiple Sclerosis - epidemiology - etiology - genetics
Risk factors
Sex ratio
Abstract
Studies in Canada have provided strong evidence that environmental factors act at a population level to influence the unusual geographical distribution of multiple sclerosis (MS). However, the available data accommodate more than one type of environmental effect. Migration studies show that changes to early environment can greatly affect risk, and there are recent indications that risk can be altered in situ. The rising incidence rates of MS in Canada implied by longitudinal increases in sex ratio place this effect in temporal context and narrow the candidates for mediating the effect of environment. Similarly, geographical patterns in Australia imply that modifiable environmental factors hold the key to preventing some 80% of cases. Genetic epidemiology provides overwhelming evidence that genetic background has an important complementary role. If genetic factors are held constant, the environment sets the disease threshold. Although these could be independent additive risk factors, it seems more likely that susceptibility is mediated by direct interactions between the environment and genes.
PubMed ID
18275928 View in PubMed
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Gestational diabetes and multiple sclerosis.

https://arctichealth.org/en/permalink/ahliterature149120
Source
Epidemiology. 2009 Sep;20(5):783-4
Publication Type
Article
Date
Sep-2009
Author
Sreeram V Ramagopalan
David A Dyment
George C Ebers
A Dessa Sadovnick
Source
Epidemiology. 2009 Sep;20(5):783-4
Date
Sep-2009
Language
English
Publication Type
Article
Keywords
Canada
Diabetes, gestational
Female
Humans
Multiple Sclerosis - epidemiology
Pregnancy
Risk assessment
Notes
Comment On: Epidemiology. 2009 Jul;20(4):611-819333127
PubMed ID
19680044 View in PubMed
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22 records – page 1 of 3.