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Age of onset in siblings concordant for multiple sclerosis.

https://arctichealth.org/en/permalink/ahliterature226576
Source
Brain. 1991 Apr;114 ( Pt 2):937-50
Publication Type
Article
Date
Apr-1991
Author
D E Bulman
A D Sadovnick
G C Ebers
Author Affiliation
Multiple Sclerosis Clinic, University of Western Ontario, London, Canada.
Source
Brain. 1991 Apr;114 ( Pt 2):937-50
Date
Apr-1991
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Age Factors
British Columbia
Diseases in Twins
Female
Humans
Male
Middle Aged
Multiple Sclerosis - genetics - physiopathology
Nuclear Family
Ontario
Regression Analysis
Time Factors
Twins, Monozygotic
Abstract
We have evaluated genetic and environmental influences in multiple sclerosis (MS) by comparing age of onset in 99 sibling pairs concordant for the disease. We used three methods of analysis: (1) comparison of mean differences in age of onset and year of onset, (2) linear regression of differences in age or year of onset vs difference in ages, and (3) intraclass correlation of age of onset which is also used for monozygotic twins concordant for MS. Comparison of the mean differences in age of onset or year of onset is found to be inappropriate and potentially misleading. No significant results were found in linear regression of the age of onset or year of onset vs differences in ages, although a trend towards onset at the same age is present. However, nontwin siblings show a significant intraclass correlation for age of onset (P less than 0.01) as is seen in genetic disorders. A stronger intraclass correlation in age of onset in concordant monozygotic twins vs concordant sibling pairs further suggests that age of onset is partly under genetic control, assuming common exposure to an environmental agent. The results give little support for common exposure to an environmental trigger in concordant MS sibling pairs. They are consistent with a mixture of random independent exposures and common exposures leading to the development of the disease, with the former predominating.
PubMed ID
2043958 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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A population-based study of multiple sclerosis in twins.

https://arctichealth.org/en/permalink/ahliterature236171
Source
N Engl J Med. 1986 Dec 25;315(26):1638-42
Publication Type
Article
Date
Dec-25-1986
Author
G C Ebers
D E Bulman
A D Sadovnick
D W Paty
S. Warren
W. Hader
T J Murray
T P Seland
P. Duquette
T. Grey
Source
N Engl J Med. 1986 Dec 25;315(26):1638-42
Date
Dec-25-1986
Language
English
Publication Type
Article
Keywords
Canada
Disease Susceptibility
Diseases in Twins
Epidemiologic Methods
Female
Humans
Magnetic Resonance Spectroscopy
Male
Multiple Sclerosis - diagnosis - genetics
Twins, Dizygotic
Twins, Monozygotic
Abstract
Results from studies of twin concordance in multiple sclerosis have not conclusively differentiated between environmental and genetic factors that determine susceptibility to the disease. Published studies that have been based on case finding by public appeal have been characterized by difficulties in ascertainment. The data reported here are from a large population-based study of multiple sclerosis in twins, in which ascertainment has been relatively unbiased and the cooperation of patients nearly complete. A total of 5463 patients attending 10 multiple sclerosis clinics across Canada were surveyed. Twenty-seven monozygotic and 43 dizygotic twin pairs were identified, and the diagnosis of multiple sclerosis was verified by examination and laboratory investigation. Seven of 27 monozygotic pairs (25.9 percent) and 1 of 43 dizygotic pairs (2.3 percent) were concordant for multiple sclerosis. The concordance rate for 4582 nontwin siblings of patients at two multiple sclerosis clinics was 1.9 percent, closely paralleling the concordance rate in dizygotic twins. To the extent that the difference in concordance rates between monozygotic and dizygotic twins indicates genetic susceptibility, the results of this study show a major genetic component in susceptibility to multiple sclerosis.
PubMed ID
3785335 View in PubMed
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A population-based study of multiple sclerosis in twins: update.

https://arctichealth.org/en/permalink/ahliterature221493
Source
Ann Neurol. 1993 Mar;33(3):281-5
Publication Type
Article
Date
Mar-1993
Author
A D Sadovnick
H. Armstrong
G P Rice
D. Bulman
L. Hashimoto
D W Paty
S A Hashimoto
S. Warren
W. Hader
T J Murray
Author Affiliation
University of British Columbia, Vancouver, Canada.
Source
Ann Neurol. 1993 Mar;33(3):281-5
Date
Mar-1993
Language
English
Publication Type
Article
Keywords
Adult
Canada
Diseases in Twins
Female
Follow-Up Studies
Humans
Male
Middle Aged
Multiple Sclerosis - genetics
Population
Twins, Dizygotic
Twins, Monozygotic
Abstract
This study is a 7.5-year follow-up of a population-based series of twins with multiple sclerosis (MS) whose mean age now exceeds 50 years. The twin pairs were identified through the Canadian nationwide system of MS clinics and were drawn from a population of 5,463 patients. After 7.5 years, the monozygotic concordance rate increased from 25.9 to 30.8% and the dizygotic-like sex concordance rate from 2.4 to 4.7%. These results are very similar to those of other population-based studies and to our own modified replication twin data reported here. We interpret the data to mean that MS susceptibility is genetically influenced, and a single dominant or even a single recessive gene is unlikely to account for this effect. The difference in concordance rates suggests that at least two or more genes are operative. These data also have important implications for the nature of the environmental effect(s) in MS susceptibility. Most monozygotic twins are discordant even after a correction for age and magnetic resonance imaging findings. This unambiguously demonstrates the powerful effect of nonheritable factors.
PubMed ID
8498811 View in PubMed
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