genetics

4 September 2010

Found: Genetic Link to "Basic" Migraine

A study of genetic data from over 50,000 people has revealed a genetic link to migraine, and is providing new information about the source of migraine and its treatment.

First of all, why are we even looking for genetic links? Well, for some time now we’ve had a reasonably good theory that migraine is genetically-based. Just a good guess? No, research up to this point has given us good reason to suspect that genetics play a large role in migraine.

Genetics and Migraine: Why we know so little

Now genetic research is still relatively young. We have a lot to learn. So it will take time to learn how various genetic factors impact our health.

However, with migraine we got a head start. Certain types of migraine have a strong relation to family ties, and have a strong genetic factor. So these have been studied an unusual amount (read: familial hemiplegic migraine). And as we’ve learnt how these genetic links work, we’ve come to believe that there are strong genetic links to other types of migraine as well. And, in fact, we’ve found that many migraineurs have certain genetic abnormalities.

Dr. Sheena K. Aurora of the Swedish Headache Center in Seattle, USA, summarized some of the past research well in the book Menstrual Migraine:

There is an increasing body of evidence for the concept of central neuronal hyperexcitability as a pivotal physiological disturbance predisposing to migraine (Welch et al., 1990). The reasons for increased neuronal excitability are likely multifactoral, with an underlying genetic basis. Genetic studies have revealed an abnormality of calcium channels that has been introduced as a potential mechanism of interictal neuronal excitability (Ophoff et al., 1996)…

In other words, this is at least one way that a genetic factor seems to make the migraine brain different – more excitable.

The 2010 Migraine Genetics Study

The recently published study came from the International Headache Genetics Consortium, a cooperation of researchers from around the world. The genetic profiles of thousands of people, both migraineurs, and non-migraineurs, were studied. The chair of the consortium, Dr Aarno Palotie, says,"This is the first time we have been able to peer into the genomes of many thousands of people and find genetic clues to understand common migraine. Studies of this kind are possible only through large-scale international collaboration — bringing together the wealth of data with the right expertise and resources — so that we could pick out this genetic variant. This discovery opens new doors to understand common human diseases."

And the results?

Patients with a DNA variant on Chromosome 8 between two genes (PGCP and MTDH/AEG-1) have a significantly greater risk of developing migraine. Why? The link appears to relate to something called glutamate.

Glutamate is a common neurotransmitter – it transmits messages in the body. In fact, it transmits pain signals. This particular DNA variant regulates glutamate levels. Is build-up of glutamate causing problems? If so, could we create a targeted treatment to prevent it?

Actually, glutamate has already been the target of research into migraine treatment. Take for example Tezampanel, and ADX10059. Namenda (memantine) is an example of a treatment already being used for migraine, which deals with glutamate.

There is still a long way to go in these studies. For one thing, it’s likely that more genetic factors will be found relating to migraine. Also, even this link needs more study. How common is it? Does it really lie at the heart of migraine in general, or only more severe versions? What about various types of chronic headache?

However, this is more evidence that we’ve come a long way in migraine research, and are getting a much better picture of what’s really going on in the body of a migraineur.

More on this study: First Genetic Link to Common Migraine Exposed

12 May 2010

Migraine and Depression: Shared Genetics

James Discoveries & Stats 0

We know that migraine and depression are comorbid – they often go together. But why? Does one cause the other? Do they cause each other? Or is there a shared factor causing both?

Migraine and Depression – a common combination

Researchers in the Department of Neurology at the Leiden University Medical Centre in the Netherlands set out to see if there was a shared genetic factor. They found 360 migraine patients, carefully diagnosed. There were 209 that had migraine without aura, and 151 that had migraine with aura.

Then they measured heritability between migraine and depression in these patients.

Heritability is a complex measurement that tells us if genetic factors contribute to something. Without going into more detail, the researchers found that there was a connection between depression and both types of migraine.

But they still had to make some adjustments – some migraine patients are on antidepressants, for example.

But even after adjustments, it was obvious that genetic factors do contribute, at least in part, to the connection between depression and migraine. The connection is even stronger in migraine with aura.

This is further confirmation of the involvement of genetics in both migraine and depression, and the reality of a medical connection between the two (far beyond "You’re just depressed because of the pain" or "You just have migraine because you’re so pessimistic"!).

For more on the study, read Shared genetic factors in migraine and depression: evidence from a genetic isolate., published in January 2010. For more on heritability, check out this brief description.

31 March 2010

Familial Hemiplegic Migraine 1 – Not Always the Same

James Discoveries & Stats 2

Familial Hemiplegic Migraine 1 (FHM1) is a rare type of migraine related to the gene locus CACNA1A. Common to FHM1 are speech, visual and sensory disturbances, headache, and loss of coordination (read more about Familial Hemiplegic Migraine here).

DNA display at
Oxford University Natural History Museum
Photo courtesy of net efekt

The fascinating thing about migraine that is familial – that clearly runs in families (although most migraine may be genetically based) is that it’s possible to study genetic connections.

Using these connections,researchers have classified different types of FHM – numbering them 1, 2 and so on (more on types of FHM).

But even within these sub-groups of a specific type of migraine, there are differences. A recent study (published in January) focused on two different CACNA1A mutations – S218L and R192Q. The former, S218L, is associated with more severe versions of FHM.

To understand the study, you need to understand that cortical spreading depression (CSD), a type of "storm" that sweeps across the brain, seems to be key to the progression of migraine symptoms. Not just in FHM, but probably in all types. (more on the science of migraine here)

The finding, in mice, was that those with the S218L mutation were far more susceptible to CSD. It took less stimuli to get one started, and often one "push" would cause multiple CSD events.

For those with the R192Q mutation, just one event was harder to start.

What does this matter? Well, obviously for those with familial hemiplegic migraine this may lead to better diagnosis and treatment.

However, it’s also doing two things for all migraine patients. First, it’s helping us understand more about how cortical spreading depression works. Second, there may be a much wider group of migraineurs that have a similar or identical mutation. Many with more common types of migraine have mutations in the gene locus CACNA1A.

In fact, it’s not only migrainuers we’re talking about. Other disorders may be involved, including those with nystagmus (involuntary movement of the eyeballs) and ataxia (unsteadiness, loss of muscle coordination), and seizures. Head trauma has also been related to this gene mutation. The connection between S218L and the calcium channels are also of interest as the study of calcium channels and migraine is of great interest in current research.

More on this study: High cortical spreading depression susceptibility and migraine-associated symptoms in Ca(v)2.1 S218L mice.
More on FHM1, seizures and head trauma
Electroencephalographic changes and seizures in familial hemiplegic migraine patients with the CACNA1A gene S218L mutation

8 June 2009

Vitamin B2, Migraine, and Genetics

James Discoveries & Stats, Treatments 0

Now we’re getting somewhere.

Recently Dr. Alexander Mauskop of the New York Headache Center reported on an Italian study related to migraine and genetics. Genetics holds a lot of promise when it comes to understanding what migraine is, and how to treat it. But we still have a long way to go.

But this study really takes us in a practical directions. Researchers discovered that the absence of a certain gene can predict how well a patient will respond to vitamin B2 (riboflavin).

Vitamin B2 has been a very helpful supplement for migraineurs, but like most things it doesn’t work for everyone (more on riboflavin here). Why not? Perhaps for many things, genetics hold the answer. Wouldn’t you love to have a test, and then be given a supplement that had a high chance of working for you, not just one that generally worked for a lot of people?

Like I said, now we’re getting somewhere.

Read Dr Mauskop’s post Genetic-based personalized medicine in headaches

14 August 2008

Migraine with Aura: the Gene that increases Stroke Risk?

James Discoveries & Stats 0

There’s been a lot of conversation about last month’s report on a genotype known as methyleneterahydrofolate reductase, or MTHFR 677TT. If you’ve read any of the reports, you may be as confused as I was at first, but let’s take a closer look.

There has been a lot of research into the connection between stroke and migraine. People with migraine, particularly specific types of migraine, do have an increased risk of stroke, according to modern research.

Now, this study involved 4577 Caucasian women who had a history of migraine (the study as a whole actually involved over 25,000 women). Over a quarter of those presently were dealing with migraine with aura.

The study followed the women for 12 years, specifically watching for cardiovascular disease.

The interesting thing about this gene is that it actually seems to decrease the risk of migraine with aura. However, if a woman has the genetic variation, and still develops migraine with aura, the risk of stroke takes a dramatic jump.

Women with the gene and migraine with aura had over three times the risk of developing cardiovascular disease. They had four times the risk of stroke, compared to women without the gene and without migraine with aura.

It’s too early to see this as a finished picture – it’s really only another small piece in the puzzle. It doesn’t look like the gene variant itself increases stroke risk – instead, there seems to be a connection between the gene and at least one type of migraine. How this all fits together is turning out to be very complex.

So what does a woman with migraine do with this information? Should she look into genetic testing? Dr. Tobias Kurth from the Harvard Medical School and one of the authors of the study says no. "At the moment, we’re not suggesting genotyping for women with migraines with aura. The consequences [of having this gene] are completely unclear right now."

Dr. Keith Siller, director of the Comprehensive Stroke Care Center at New York University’s Langone Medical Center explains that this may not even be the "right" gene – there is a connection, but it may be another gene causing the problem.

As we try to understand the link between stroke and migraine, there are a couple of things to keep in mind. First, the increased risk from migraine alone is not a reason to panic. Second, it is a reminder that we need to pay special attention to decreasing our risk in other ways – such as paying attention to our lifestyle and what we put in our bodies.

Dr. Kurth recommends: "Doctors should try to reduce heart disease risk factors and advise young women who experience migraine with aura not to smoke and to consider birth control pill alternatives as these increase the risk of ischemic vascular problems."

And we wait until the puzzle is more complete…

For more, read Gene May Put Women With Migraine At Increased Risk Of Heart Disease And Stroke, Gene Linked To Migraine and Increased Stroke Risk, and Interrelationships among the MTHFR 677C>T polymorphism, migraine, and cardiovascular disease