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Study Identifies Factors in Risk
of Siblings Developing Multiple Sclerosis
Medical Update Memo
May 8, 1998
Summary
A study of 1,896 people with multiple sclerosis registered
at the MS Clinic, University of British Columbia, shows that
the risk of developing MS among brothers and sisters can be
more accurately predicted by several factors. These include
the age at which the index case (the person registered at the
MS Clinic) developed MS, the gender of siblings (brothers and
sisters) and whether a parent also has multiple sclerosis. Information
from the study should be useful for better genetic counselling
purposes. The study which was published in the March 1998 issue
of Neurology was conducted by A. Dessa Sadovnick, Ph.D., University
of British Columbia; Irene M.L. Yee, M.Sc., University of British
Columbia; George C. Ebers, M.D., University of Western Ontario;
and Neil J. Risch, Ph.D., Stanford University. It was supported
by the MS Scientific Research Foundation and the Multiple Sclerosis
Society of Canada.
Background
The development of MS is believed to be influenced by both
genetic and environmental (non-genetic) factors. It has long
been observed that MS prevalence varies by gender, age, geography
and ethnic background. This study, published in the March 1998
issue of Neurology, presents additional data on the risks of
brothers and sisters of a person with MS to also develop the
disease. The size of this study -- 1,896 people with MS and
8,878 of their first-degree relatives (siblings and parents)
-- enabled investigators for the first time to look at five
variables to determine if they had any affect on family risk
of MS. Three of the variables were found to interact and to
be particularly significant. They are:
- The gender of the sibling of the index
case
- Whether one of the parents had MS
- Age of onset of MS in the index case
The investigators collected data from nearly
2,000 Caucasian individuals with MS and their first-degree family
members from September 1980 to January 1986. The "index
case" was the first member of a family to be registered
with the MS Clinic in Vancouver during the period of the study.
Adopted and non-Caucasian people with MS were excluded as were
people who came to the clinic specifically because they had
concerns about familial MS.
Specific findings
Gender of the sibling -- The study supports earlier observations
that women are affected by MS almost twice as often as men.
Sisters of males and females with MS had an overall unadjusted
lifetime rate of MS of 2.3% and 2.7% respectively. In comparison,
brothers of males and females had an overall unadjusted lifetime
risk of 1.5% and 0.6% respectively. Overall, the life-time risk
for sisters of index cases was about 2.5 times greater than
that for brothers. The gender of the index case did not seem
to be significant in determining increased family risk.
Gender of the sibling and one parent affected
by MS -- Family risk to siblings is increased dramatically if
one of the parents of the index case also has MS. Sisters of
index cases who had a parent with MS had an age adjusted rate
of 8.1%; sisters of index cases without an affected parent had
an age adjusted rate of 2.4%. Brothers of index cases who had
an affected parent had an age adjusted rate of 3.4% while brothers
of index cases without an affected parent had an adjusted rate
of 0.8%. Having a parent and a sibling with MS increases the
risk of developing MS for other brothers and sisters about four
times, say the investigators.
Parent affected by MS, gender of the sibling
and index case age at onset -- Equally dramatic in its impact
on family risk was the age at which the index case developed
MS. The study found that the risk to siblings is increased up
to five times if the index cases was 20 years old or less when
diagnosed with MS, compared to the risk for siblings of people
who were diagnosed at 40 years of age or older. When age adjusted,
the lifetime risk for siblings with an affected parent and a
brother or sister with MS is about four times more, compared
to those without an affected parent.
Dr. Sadovnick cautioned that despite the
increased risks shown in the study, the actual lifetime rate
are still low -- well under 5% for brothers and sisters of people
who have MS. The lifetime rate of developing MS for the general
population is 0.2%.
The University of British Columbia study
is part of the large Canadian Collaborative study of Genetic
Susceptibility in Multiple Sclerosis headed by Drs. Sadovnick
and Ebers. It involves all 15 MS clinics in Canada and is funded
by the Multiple Sclerosis Scientific Research Foundation, which
is related to the Multiple Sclerosis Society of Canada.
Earlier published findings from the collaborative
study and from other studies have suggested that as many as
six genes may be involved in determining genetic susceptibility
in MS and, in particular, the HLA region on chromosome 6 may
be implicated. The University of British Columbia study does
not necessarily support those findings since similar findings
have been shown in other diseases in which genetic susceptibility
is affected by one gene, but the new data can be used for better
genetic counselling of people who have MS and to identify people
who are at a higher risk for developing the disease. If people
at higher risk are diagnosed earlier, they may be able to benefit
from treatments currently available that may modify or slow
the progress of MS.
Disclaimer
The Multiple Sclerosis Society of Canada is an independent,
voluntary health agency and does not approve, endorse or recommend
any specific product or therapy but provides information to
assist individuals in making their own decisions.
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