Largest genetic study of migraine to date reveals new genetic risk
factors

Date:
February 3, 2022
Source:
University of Helsinki
Summary:
Scientists identified more than 120 regions of the genome that
are connected to risk of migraine. The groundbreaking study helps
researchers better understand the biological basis of migraine and
its subtypes and could speed up the search for new treatment of
the condition, which affects over a billion individuals worldwide.



FULL STORY ==========================================================================
An international consortium of leading migraine scientists identified
more than 120 regions of the genome that are connected to risk of
migraine. The groundbreaking study helps researchers better understand
the biological basis of migraine and its subtypes and could speed up the
search for new treatment of the condition, which affects over a billion individuals worldwide.


==========================================================================
In the largest genome study of migraine yet, researchers have more than
tripled the number of known genetic risk factors for migraine. Among
the identified 123 genetic regions are two that contain target genes of recently developed migraine-specific drugs.

The study involved leading migraine research groups in Europe, Australia
and the United States working together to pool genetic data from more
than 873,000 study participants, 102,000 of whom had migraine.

The new findings, published on February 3, 2022 in the journal
NatureGenetics, alsouncovered more of the genetic architecture of migraine subtypes than was previously known.

Neurovascular mechanisms underlie migraine pathophysiology Migraine is a
very common brain disorder with over a billion patients worldwide. The
exact cause of migraine is unknown, but it is believed to be a
neurovascular disorder with disease mechanisms both within the brain
and the blood vessels of the head.



========================================================================== Previous research has shown that genetic factors contribute significantly
to the migraine risk. However, it has long been debated whether the two
main migraine types -- migraine with aura and migraine without aura --
share similar genetic background.

To gain more insight into the specific risk genes, researchers from the International Headache Genetics Consortium assembled a large genetic
dataset to conduct a genome-wide association study (GWAS), looking for
genetic variants that were more common in those who had migraine in
general, or one of the two main migraine types.

The results demonstrated that migraine subtypes have both shared risk
factors and risk factors that appear specific to one subtype. The analyses highlighted three risk variants that appear specific to migraine with
aura and two that appear specific to migraine without aura.

"In addition to implicating tens of new regions of the genome for
more targeted investigation, our study provides the first meaningful opportunity to evaluate shared and distinct genetic components in
the two main migraine subtypes," said the first author of the study,
Heidi Hautakangas from the Institute for Molecular Medicine Finland,
University of Helsinki.

Furthermore, the results supported the concept that migraine is brought
about by both neuronal and vascular genetic factors, strengthening the
view that migraine truly is a neurovascular disorder.



========================================================================== Potential to point to new therapies against migraine As migraine is
globally the second largest contributor to years lived with disability,
there is clearly a large need for new treatments.

A particularly interesting finding was the identification of genomic
risk regions containing genes that encode targets for recently developed migraine- specific therapeutics.

One of the newly identified regions contains genes (CALCA/CALCB)
encoding calcitonin gene-related peptide, a molecule involved in migraine attacks and blocked by the recently introduced CGRP inhibitor migraine medications. Another risk region covers the HTR1F gene encoding serotonin
1F receptor, also a target for new migraine-specific medications.

Dr. Matti Pirinen, a group leader from the Institute for Molecular
Medicine Finland, University of Helsinki, who led the study, commented:
"These two new associations near genes that are already targeted by
effective migraine drugs suggest that there could be other potential drug targets among the new genomic regions, and provide a clear rationale for
future genetic studies with even larger sample sizes." The study was a
joint effort between research groups from Australia, Denmark, Estonia,
Finland, Germany, Iceland, Netherlands, Norway, Sweden, UK and USA.

special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by University_of_Helsinki. Original
written by Mari Kaunisto. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Heidi Hautakangas, Bendik S. Winsvold, Sanni E. Ruotsalainen, Gyda
Bjornsdottir, Aster V. E. Harder, Lisette J. A. Kogelman, Laurent F.

Thomas, Raymond Noordam, Christian Benner, Padhraig Gormley,
Ville Artto, Karina Banasik, Anna Bjornsdottir, Dorret I. Boomsma,
Ben M. Brumpton, Kristoffer So/lvsten Burgdorf, Julie E. Buring,
Mona Ameri Chalmer, Irene de Boer, Martin Dichgans, Christian
Erikstrup, Markus Fa"rkkila", Maiken Elvestad Garbrielsen, Mohsen
Ghanbari, Knut Hagen, Paavo Ha"ppo"la", Jouke-Jan Hottenga, Maria
G. Hrafnsdottir, Kristian Hveem, Marianne Bakke Johnsen, Mika
Ka"ho"nen, Espen S. Kristoffersen, Tobias Kurth, Terho Lehtima"ki,
Lannie Lighart, Sigurdur H. Magnusson, Rainer Malik, Ole Birger
Pedersen, Nadine Pelzer, Brenda W. J. H. Penninx, Caroline Ran,
Paul M. Ridker, Frits R. Rosendaal, Gudrun R. Sigurdardottir, Anne
Heidi Skogholt, Olafur A. Sveinsson, Thorgeir E. Thorgeirsson,
Henrik Ullum, Lisanne S. Vijfhuizen, Elisabeth Wide'n, Ko Willems
van Dijk, Irene de Boer, Arn M. J. M. van den Maagdenberg, Arpo
Aromaa, Andrea Carmine Belin, Tobias Freilinger, M. Arfan Ikram,
Marjo-Riitta Ja"rvelin, Olli T.

Raitakari, Gisela M. Terwindt, Mikko Kallela, Maija Wessman, Jes
Olesen, Daniel I. Chasman, Dale R. Nyholt, Hreinn Stefa'nsson,
Kari Stefansson, Arn M. J. M. van den Maagdenberg, Thomas Folkmann
Hansen, Samuli Ripatti, John-Anker Zwart, Aarno Palotie, Matti
Pirinen. Genome-wide analysis of 102,084 migraine cases identifies
123 risk loci and subtype-specific risk alleles. Nature Genetics,
2022; DOI: 10.1038/s41588-021-00990-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220203122535.htm

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