Largest-ever family study of migraine provides new insight into the disease

May 03, 2018

The results of the largest genetic family study on migraine thus far were published online in the journal Neuron today, May 3. The study was based on medical history and genetic data of 1,589 Finnish migraine families with more than 8,300 individuals. Researchers from the University of Helsinki, Helsinki University Central Hospital and the Broad Institute of MIT and Harvard coordinated the study.

Migraine is one of the most common brain disorders worldwide, affecting approximately 15-20% of the adults in developed countries. In many families there are much more migraine patients than would be expected by chance alone. The molecular mechanisms of migraine and the reasons for familial clustering remain poorly understood.

By studying more than 59.000 migraine patients, the researchers behind this study have earlier identified over 40 significant genetic risk variants that predispose individuals to migraine. In addition, this earlier study provided evidence of hundreds or even thousands of additional variants that have a smaller impact on migraine risk. In the present study, the team combined information from all these implicated risk variants and calculated a personal genetic risk score for each of the study participants.

This genetic risk score was used to estimate and compare the genetic burden conferred by common variants in different migraine patient subgroups.

"Both rare, high-impact and common genetic variants with smaller impact could contribute to the familial aggregation of migraine. In this study, we wanted to find out which one is more important and whether the genetic load is higher in certain types of migraine", said Dr. Padhraig Gormley from the Broad Institute of MIT and Harvard, the first author of the study.

One third of migraine patients experience additional neurological symptoms during attacks, called aura. The Finnish family migraine cohort contained 2,420 patients with a diagnosis of migraine with typical aura and 540 patients diagnosed with less common hemiplegic aura symptoms.

The family cohort was also compared against another large Finnish sample, the FINRISK population cohort with close to 15,000 participants, including 1,100 with migraine.

The researchers observed an overall increased genetic risk score in familial migraine cases compared to general migraine cases from the population and clear differences of the common variant load across different migraine subtypes.

Of special interest was the contribution of common and rare genetic variation to hemiplegic migraine, a disease primarily thought to be caused by rare pathogenic variants in three genes. Even for this migraine subgroup, the results showed that the combined effect of common risk variants was greater than the effect of rare mutations. In fact, of all the migraine subtypes analyzed, the genetic load was highest in this group of patients.

Further analyzes showed that the genetic risk score was also associated with the age of onset of migraine headaches. Genetic load was significantly higher in migraine cases where headache onset occurred before 20 years of age compared to individuals with later onset.

"Our study supports the hypothesis that migraine subtypes are genetically heterogeneous diseases, and that common polygenic variation significantly contributes to the aggregation of the disease in families, both for common and rare migraine subtypes", concluded Professor Aarno Palotie from the Institute for Molecular Medicine Finland FIMM at the University of Helsinki.

"We were surprised by the impact of the common variants in these families. However, much of the genetic predisposition to migraine still remains unexplained. It is likely that further studies will reveal more common and rare migraine risk variants."
-end-
The study was conducted in collaboration with members of the International Headache Genetics Consortium, the 23andMe research team and Merck & Co., Inc., Kenilworth, NJ, USA.

University of Helsinki

Related Migraine Articles from Brightsurf:

Disparities in migraine by sexual orientation
Survey data were used to examine the association between sexual orientation (exclusively heterosexual, mostly heterosexual, lesbian, gay or bisexual) and migraine.

Can you paint your migraine?
'Can you draw me a picture of your headache?' may sound like an unusual question - but drawings of headache pain provide plastic surgeons with valuable information on which patients are more or less likely to benefit from surgery to alleviate migraine headaches.

Acupuncture can reduce migraine headaches
Acupuncture can reduce migraine headaches compared to both sham (placebo) acupuncture and usual care, finds a new trial from China published by The BMJ today.

Migraine rats, medical facts
Migraine mechanisms are still far from being fully understood. Escalating data from animal models are 'fact-checking' the neurophysiological and behavioral correlates of the migraine experience in humans, and how they may be affected by current anti-migraine drugs or might translate into new therapies.

Connecting the dots in the migraine brain
This dMRI study pointed to the structural strengthening of connections involving subcortical regions associated with pain processing and weakening in connections involving cortical regions associated with hyperexcitability may coexist in migraine.

Predictors of chronic migraine
A review and meta-analysis found predictors of chronic migraine. Depression, high frequency attacks, medication overuse and allodynia increased the chances for new onset chronic migraine, while annual income -- US$ 50,000 showed a protective effect.

On nitroglycerin, cardiovascular homeostasis and...bam, migraine!
Researchers in Leiden, The Netherlands, found an exaggerated cardiovascular response to nitroglycerin infusion in migraine patients, suggesting an elevated systemic sensitivity to this compound in this population.

All roads lead to migraine
Dr. Samaira Younis, from the Danish Headache Center in Copenhagen, Denmark, shares her research results, which suggests there are no differences between migraine attacks clinical characteristics following administration of 2 different compounds in patients, CGRP and sildenafil, meaning they share common cellular signaling pathways.

Running away from exercise: The curious case of migraine
In spite of the widespread recommendation for regular physical activity as a strategy to manage migraine, for some patients, exercise can instead trigger migraine attacks.

Migraine prevention in children and adolescents
Two medicines already used to prevent migraine in adults also showed efficacy in adolescents with migraine.

Read More: Migraine News and Migraine Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.