migraine genetics

25 June 2013

Massive Genetic Study Zeros in on Migraine

In a massive study led by an international team of researchers, 5 new genetic regions linked to migraine have been discovered.

And when I say massive, I mean massive. Researchers working with the Wellcome Trust Sanger Institute took the results of 29 different genetic studies, involving over 100,000 samples from both migraine patients and controls.

So in plain numbers, what was discovered?

5 genetic regions linked to migraine onset, discovered for the first time.
12 genetic regions total associated with migraine susceptibility
134 genetic regions that are possibly associated to migraine susceptibility

Now, imagine that migraine involves a web of factors, including genetic factors. You can’t just say that “this one” causes migraine, and change it. You have to understand how things are linked together – how they impact each other – how they interact.

And that’s just what these researchers are doing. For example, 8 of the 12 regions were related to maintaining healthy brain tissue and function.

Some also related to an issue called oxidative stress. This relates to the body’s ability to detoxify and heal.

This is “early release” information – just a teaser – because the work is far from done. The research will be continuing, and will only be half done by the end of 2014.

But working together (patient, doctor, researcher), we will likely come up with a lot more insight into migraine even before that.

For more, read: Getting to grips with migraine

7 May 2013

Another Genetic Link to Migraine?

James Discoveries & Stats, News 0

Researchers at the University of California have discovered a new genetic link to migraine – and a rare sleep disorder – that may get us closer to the cause of migraine than ever before.

First, a note. Last week on Facebook, Damien Higgins posted the following: There was Migraine News today that made many of the international news channels and you havnt even mentioned it!!! this page is not exactly on the ball, is it!!!http://news.sky.com/story/1085914/hope-for-migraine-sufferers-after-genes-find

Well, I have no particular excuse for not mentioning this story sooner, other than to say that this website has not yet reached the level of perfection that I or Damien may want!

That being said, many stories hit “international news” and are really hardly worth mentioning, in my opinion. Honestly, a lot of migraine news is old news, poorly reported, blown out of proportion, or in reality not useful. And sometimes it’s worth taking the extra time to research the news a little more before repeating the same thing here.

Regarding genetics and migraine, we’ve discussed a lot of discoveries here. In fact, back in 2010 we talked about a similar news story – Found: Genetic Link to “Basic” Migraine

We’ve also talked about something critical to understand – Migraine: Why Genetic Studies haven’t Solved all our Problems.

In Damien’s defence, however, this news story is worth mentioning. And I won’t claim that the Sky news report is overblown, although most migraineurs are probably tired of seeing the same old headline – “Hope for Migraine Sufferers…”! 🙂

Study Overview

First, we need to be cautious about claiming that we’ve “finally found the genetic cause of common migraine”. This is not the first time genetic mutations have been linked with common forms of migraine. There are some unique things about this study which we’ll discuss in a moment, but it’s a tricky thing to prove that a genetic mutation is the cause or even related to “most” migraine attacks.

Researchers were actually looking at two conditions: Migraine and Advanced Sleep Phase Syndrome. This sleep syndrome causes you to go to sleep earlier (ie in the evening) and get up earlier (ie between 1 and 5 am).

Researchers found two families in which many members had both conditions (in this case, the sleep disorder would be called familial advanced sleep phase syndrome).

To make a long story short, it was discovered that two related gene mutations were highly associated with both conditions.

Now mice who had one of these mutations (CKIÎ´-T44A) were also researched. These mice had a lower threshold for cortical spreading depression (CSD), a storm that sweeps across the brain that is considered a key part of the migraine chain reaction. In other words, they were more likely to get CSD.

These mice were more sensitive to pain, and astrocytes (certain neurological cells) showed increased calcium signalling, which may relate to parts of the migraine reaction as well.

Now the research on CKIÎ´-T44A and the mice and migraine is not new. Neither is the link between these two mutations and advanced sleep phase syndrome. However, the link with the two mutations and the two conditions – migraine and advanced sleep phase syndrome is.

You might be a little underwhelmed that we’re just talking about two families, and a rare sleep disorder, and just another two mutations after we’ve already linked others with migraine.

However, this is how a lot of good research starts.

These mutations are linked. And the most important finding may not be the mutations themselves, but what they point to.

For one thing, they both influence a special protein known a connexin 43 (Cx43). Even if these particular genetic mutations don’t turn out to be common in migraineurs, there could be other factors that are impacting Cx43, and so that might be the direction that future research takes.

I’ve intentionally avoided getting into all the specific mechanisms of these mutations in order to focus on the practical implications. But if you’re interested in the more technical aspects, you can read the study abstract: Casein Kinase IÎ´ Mutations in Familial Migraine and Advanced Sleep Phase and a discussion of the findings at Gene Mutations Tied to Migraine, Sleep Disorder.

27 September 2011

Mutiny on the Bounty and Migraine (video)

James News 0

You don’t usually think of those two as related, do you? Well, researchers at Griffith University, where a lot of research is being done into migraine, have indeed taken notice of the descendants of the mutineers and the prevalence of migraine disease among the people today. Compared to the general population, the prevalence of migraine is more than double.

Studying this group of people is providing new insights into the genetics of migraine, as is summarized by Ms Hannah Cox in this brief video.

4 September 2010

Found: Genetic Link to "Basic" Migraine

James Discoveries & Stats, News 0

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 July 2008

Genetic mutations, migraine auras, and epilepsy

James Discoveries & Stats, Medications 0

Genetic research into migraine continues to suggest directions of treatment that haven’t been widely considered before. The latest studies out of the Vanderbilt University Medical Center in the USA are doing just that, and also increasing interest in studying links between migraine and epilepsy.

Here’s the story in brief. The study is about a rare form of migraine known as Familial Hemiplegic Migraine type 3. Studies of FHM have helped us understand genetic markers in the past. Often the focus has been on what are called calcium channels in the body.

But the new research is focusing on something different – sodium channels. A mutant gene causes problems with the normal functioning of the calcium channel in the body. Sodium channels act as "gateways" to allow sodium into the cell. When the channel gets "stuck" open, too much sodium gets through.

It may be that the genetic problem is involved in causing the cortical spreading depression in the brain, which comes early in the migraine chain of events.

Though FHM3 is not a common form of migraine, there may be some similarities here with more common forms. And it looks like drugs that act as sodium channel blockers may be worth further investigation.

The team at Vanderbilt University was studying the same gene for epilepsy issues. Finding a common cause between migraine and epilepsy could strengthen the suspected link between the two diseases.

The Vanderbilt Medical Center has an article on this research published yesterday if you want more depth – Mutations reveal clues to biological basis of migraines.