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Twin Study Sheds Interesting Light on MS
Samuel Pleasure, MD, Neurology, 11:58AM May 12, 2010
MS is a prototypical complex disease. The occurrence of MS seems to be related to
both inherited susceptibility and an environmental trigger of some kind. In recent
years whole genome surveys of genes associated with the occurrence of MS have found
a number genetic factors that clearly modify the risk of developing the disease.
Many of these susceptibility genes are ones involved in modulation of immune responses,
which makes sense given the strong association of auto-
A new study by Baranzini and colleagues gives another important perspective on the
question of MS genetic susceptibility vs environmental triggering. In the interests
of academic disclosure, Dr. Baranzini is a colleague of mine at UCSF, as are some
of the other authors, but the importance of this study is pretty uniformly agreed
upon as it was published in Nature and was featured on the cover. In this study the
authors had the opportunity to examine a monozygotic twin pair that is discordant
for MS. Obviously monozygotic twin studies are one of the more stringent ones for
assessing the role of genetics in disease occurrence. The twins are genetically identical,
yet for MS the established risk of disease concurrence for monozygotic twins is generally
about 25%. This has previously helped to establish the strong role of genetic factors,
but also indicates quite strongly that there must be non-
One potential explanation for the lack of concurrence in the twins could be that
they have de novo mutations that might be associated with disease. In the study by
Baranzini et al. they sequenced the full genome of both twins and found no evidence
for this explanation. Where the study then went further was to compare the twins
(as well as two other pairs of discordant twins) in a number of other ways. They
found no significant difference in the expression of over 19,000 genes in CD4+ T-
What does this all mean? Well, further study is obviously needed but the negative
results of these studies, showing that there are essentially no observable genetic
differences between twins discordant for MS, is very strong evidence for some sort
of environmental trigger. This trigger (which could be a virus, other infection,
chemical exposure, etc, etc) must be something that affects one twin and not the
other, leading to one twin developing disease and the other not. Of course both twins
would be equally genetically susceptible to disease but the exposure to this environmental
trigger or the timing or severity of the exposure must be where the difference lies.
At some level of course there must be expression differences in some genes between
the twins in some tissues because one twin is suffering from the typical injury pattern
of MS and the other isn't, but there isn't evidence for such differences in CD4+
T-
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