First gene link to common migraine

In the paper today: … 5911696634

[size=150]First gene link to common migraine[/size]

GENE detectives say they have found the first inherited link to common types of migraine, a finding that boosts hopes for new drugs to curb this painful and costly disorder.

Scientists from 40 medical centres pored over the genetic profiles of more than 50,000 people, comparing those who suffered badly from migraines with others who were otherwise healthy.

What came up in the net was a tiny, but tell-tale variant of DNA that boosts the risk of getting migraines by around a fifth.

“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,” Aarno Palotie, head of the International Headache Genetics Consortium at Britain’s Wellcome Trust Sanger Institute, which led the study, said today.

Previous research has found links for some extreme, but mercifully rare, forms of migraine, but this is the first to pinpoint an association for common types of the disease.

The tiny genetic variant, or allele, is called rs1835740.

Lying on Chromosome 8 between two genes, PGCP and MTDH/AEG-1, it allows a messenger chemical called glutamate to accumulate in junctions between brain cells, and this unleashes the migraine, the scientists believe.

If so, drug engineers have a tempting target in preventing glutamate buildup, they hope.

The paper, published online in the journal Nature Genetics, stated that migraine affects 17 per cent of European women and eight per cent of men.

The UN’s World Health Organisation (WHO) ranks migraine in the top 20 diseases in terms of “years lived with disability”, a benchmark of handicap. A US estimate put migraine’s economic cost on par with diabetes.

The study first compared the genome of more than 3000 migraine sufferers in Finland, Germany and The Netherlands against that of about 10,000 non-sufferers.

These results were then compared in a second phase with the genomes of a second batch, comprising 3000 migraine patients and more than 40,000 otherwise healthy people.

The study found rs1835740 to be one of several connecting genetic cogs in regulating glutamate levels.

The allele alters the MTDH/AEG-1 gene, which in turn affects a gene called EAAT2.

The EAAT2 gene controls a protein that is responsible for clearing glutamate from the brain synapses. This protein has previously been linked with epilepsy, schizophrenia and various mood and anxiety disorders.

The authors say further work is needed to confirm the findings and see whether other genetic culprits abound.

Patients in the study were recruited mainly from specialist headache clinics, which means they are likely to represent only the more extreme end of those who suffer from common migraines, said Gisela Terwindt of Leiden University Medical Centre in The Netherlands.

“In the future, we should look at associations across the general population, including also people who are less severely affected,” she said.

Migraine is believed to occur when inflammatory chemicals are released around the nerves and blood vessels in the head, inducing pain that can be excruciating. It is sometimes accompanied by nausea and hyper-sensitivity to light and sound.

Common migraines fall into two categories - those with an “aura”, or shimmering circle, seen by the sufferer, and those without.

Sufferers tend to be aged 35 to 45, although the frequency and duration of the attacks can vary widely.


Any idea what they mean by the reference to “rarer forms of migraine”?

I find it interesting that they describe a visual aura as a shimmering circle. I did not have the impression that the term was restricted to anything so specific.

Thaks Scott.

I am so happy to hear that this is being worked on, researched and having some breakthrough. I think as time goes on, they will really figure this out. Hopefully sooner than later!!
Some tests that have been taken on me that could possibly be linked to this, is PFO (hole in heart) and testing double positive on the MTHFR gene…which predisposes one to increased stroke/cardiovascular
problems. … _reductase

sometimes digging up this stuff is scary!!


Kelley - Do you have PFO? Awhile ago I was looking up some research being done on this and I wonder if they have found it to be a cause of migraines? I am kind of curious if I have this and if getting it closed would improve our condition?

Yes, when I first saw a neurologist for this “condition”…he gave me a paper on supplements for “migraine”…and Ithought he was nuts. I never had a headache in my life. I just had that crazy lightheaded brain fog 24/7. Then he sent me
for a ton of blood work to check for anything and everything, MRI/CT scan and then the bubble test for PFO…I tested positive for it and then had to go to hospital to have it confirmed via a camera down the esophagus (sp?) and take a photo
of the hole…which is more of a slit I think. The doc was telling me that closing it would solve my problems…I spoke to 3 cardiologists and none of them thought it would make a difference. There are many studies about this and I actually talked
to a few people who had the hole closed and were super happy that they did. Some of them had strokes as well.
So I am freaking out thinking I Need to have heart surgery…went online to Mayo and Cleveland Clinic to look into it (btw, they said it was a quick painless and easy procedure at the neuro office…) and saw that it really is quite a big ordeal.
I gathered all this info to go back and talk to my neuro about why I didn’t think closure would be the answer, and when I went back for my follow up, he totally changed his tune from saying I Needed to get it closed to fix my condition, to saying the latest studies say they don’t recommend closure for Migraine.
so!! All that stress for nothing!
That’s my story…

This release just come off embargo. (It is not specific to MAV.)

Findings published in Epilepsia, a journal of the International League Against Epilepsy (ILAE), indicate that having a strong family history of seizure disorders increases the chance of having migraine with aura (MA).

Medical evidence has established that migraine and epilepsy often co-occur in patients; this co-occurrence is called “comorbidity.” Previous studies have found that people with epilepsy are substantially more likely than the general population to have migraine headache. However, it is not clear whether that comorbidity results from a shared genetic cause.

“Epilepsy and migraine are each individually influenced by genetic factors,” explains lead author Dr. Melodie Winawer from Columbia University Medical Center in New York. “Our study is the first to confirm a shared genetic susceptibility to epilepsy and migraine in a large population of patients with common forms of epilepsy.”

For the present study, Dr. Winawer and colleagues analyzed data collected from participants in the Epilepsy Phenome/Genome Project (EPGP)—a genetic study of epilepsy patients and families from 27 clinical centers in the U.S., Canada, Argentina, Australia, and New Zealand. The study examined one aspect of EPGP: sibling and parent-child pairs with focal epilepsy or generalized epilepsy of unknown cause. Most people with epilepsy have no family members affected with epilepsy. EPGP was designed to look at those rare families with more than one individual with epilepsy, in order to increase the chance of finding genetic causes of epilepsy.

Analysis of 730 participants with epilepsy from 501 families demonstrated that the prevalence of MA—when additional symptoms, such as blind spots or flashing lights, occur prior to the headache pain— was substantially increased when there were several individuals in the family with seizure disorders. EPGP study participants with epilepsy who had three or more additional close relatives with a seizure disorder were more than twice as likely to experience MA than patients from families with fewer individuals with seizures. In other words, the stronger the genetic effect on epilepsy in the family, the higher the rates of MA. This result provides evidence that a gene or genes exist that cause both epilepsy and migraine.

Identification of genetic contributions to the comorbidity of epilepsy with other disorders, like migraine, has implications for epilepsy patients. Prior research has shown that coexisting conditions impact the quality of life, treatment success, and mortality of epilepsy patients, with some experts suggesting that these comorbidities may have a greater impact on patients than the seizures themselves. In fact, comorbid conditions are emphasized in the National Institutes of Health Epilepsy Research Benchmarks and in a recent report on epilepsy from the Institute of Medicine.

“Our study demonstrates a strong genetic basis for migraine and epilepsy, because the rate of migraine is increased only in people who have close (rather than distant) relatives with epilepsy and only when three or more family members are affected,” concludes Dr. Winawer. “Further investigation of the genetics of groups of comorbid disorders and epilepsy will help to improve the diagnosis and treatment of these comorbidities, and enhance the quality of life for those with epilepsy.”