A groundbreaking study of the migraine genome reveals new genetic risk factors

An international consortium of leading migraine scientists has identified more than 120 genome regions that are associated with migraine risk.

The groundbreaking study helps researchers better understand the biological basis of migraine and its subtypes and can accelerate the search for new treatments for the disease, which affects more than a billion people worldwide.

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

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

New findings published February 3, 2022 in the journal Nature Genetics too discovered more genetic architecture of migraine subtypes than was previously known.

The pathophysiology of migraine is based on neurovascular mechanisms

Migraine is a very common brain disease with more than a billion patients worldwide. The exact cause of migraine is unknown, but it is believed to be a neurovascular disease with disease mechanisms in both the brain and the blood vessels of the head.

Previous studies have shown that genetic factors significantly contribute to migraine risk. However, it has long been debated whether the two main types of migraine – migraine with aura and migraine without aura – have a similar genetic background.

To gain a better understanding of specific risk genes, researchers from the International Headache Genetics Consortium gathered a large set of genetic data for the General Genome Association (GWAS), looking for genetic variants that were more common in those who suffered from migraine in general, or one of two major types of migraines.

The results showed that migraine subtypes have both common risk factors and risk factors specific to one subtype. The analysis identified three risk options that are specific to migraines with aura and two that are specific to migraines without aura.

“In addition to involving dozens of new genome areas for more focused research, our study provides the first significant opportunities to assess common and different genetic components in the two major migraine subtypes,” said study lead author Heidi Hautakangas of the Institute of Molecular Medicine, University of Finland, University.

In addition, the results supported the concept that migraine is caused by both neuronal and vascular genetic factors, reinforcing the notion that migraine is indeed a neurovascular disorder.

The potential to point to new treatments for migraines

Since migraine is the world’s second leading cause of years of disability, there is clearly a great need for new treatments.

A particularly interesting finding was the identification of genomic risk areas containing genes encoding targets for newly developed migraine-specific agents.

One of the recently discovered regions contains genes (CALCA / CALCB), which encodes a peptide linked to the calcitonin gene, a molecule involved in migraine attacks and blocked by newly administered CGRP inhibitors, migraine drugs. Another risk region covers HTR1F the gene encoding the serotonin 1F receptor is also a target for new migraine-specific drugs.

Dr Matija Pirinen, head of the team at the Institute of Molecular Medicine in Finland, University of Helsinki, who led the study, commented: among new genomic regions, and provide a clear rationale for future genetic research with even larger sample sizes ”.

Reference: “Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles,” by Heidi Hautakangas, Bendick S. Winswald, Sunny E. Ruotsalainen, Guido Björnsdottir, Aster, W. E. Hard. Lizette Lougel. Thomas, Raymond Nordham, Christian Banner, Podreig Gormley, Will Artto, Karina Banasik, Anna Bjornsdottir, Doret I. Bumsma, Ben M. Brampton, Christopher Solvesten Burgdorf, Julie E. Buring, Mona Amery Chalmer, Irene deer, Irene de Dichgan Christian Erikstrup, Marcus Farkkil, Maiken Elvest Garbrielsen, Mohsen Gonbari, Knut Hagen, Paava Hepel, Youke-Jan Hotenga, Maria G. Hrafensdotir, Christian Hveem, Marianne Bake Erenhen, Terhesen, Lani Ligart, Sigurdur H. Magnusson, Rainer Malik, Ole Birger Pedersen, Nadine Peltzer, Brenda U.H. Penniks, Caroline Run, Paul M. Rydker, Fritz R. Roosendaal, Gudrun R. Sigurdardottir, Anne Heidi Skagholt, Olafur A. Sveins E. Th orgeirsson, Henrik Ullum, Lisanne S. Vijfhuizen, Elisabeth Widéj, Ko Wilkels van D Headache Genetics Consortium, HUNT All-in Headache, Danish Blood Donor Study Genomic Cohort, Arpo Aromaa, Andrea Carmine Belin, Tobias Ar Freilifan, Tobias Ar Freilifan, Marjo-Riitta Järvelin, Olli T. Raitakari, Gisela M. Terwindt, Mikko Kallela, Maija Wessman, Jes Olesen, Daniel I. Chasman, Dale R. Nyholt, Hreinn Stefánsson, Kari Stefansson, Arn MJM van den Maagdenberg, Samuli Ripati, John-Anker Schwart, Aarna Palotti and Mother Pirinen, February 3, 2022, Genetics of nature.
DOI: 10.1038 / s41588-021-00990-0

The study was a joint effort of research teams from Australia, Denmark, Estonia, Finland, Germany, Iceland, the Netherlands, Norway, Sweden, the UK and the US. A groundbreaking study of the migraine genome reveals new genetic risk factors

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