More than 120 areas of the genome have been linked to migraine risk, according to an international group of renowned migraine researchers. The ground-breaking findings will aid researchers in better understanding the biological foundation of migraine and its subtypes, perhaps speeding up the quest for new migraine treatments. Migraine affects over a billion people worldwide.
Researchers have more than tripled the number of known genetic risk factors for migraine in the largest genome study of migraine ever conducted. Two of the 123 genomic areas discovered include target genes for migraine-specific medicines that have recently been developed.
Leading migraine research organizations from Europe, Australia, and the United States collaborated in the study, pooling genetic data from over 873,000 study participants, 102,000 of whom had migraine.
The new findings, which were published in the journal Nature Genetics on February 3, 2022, revealed a lot more about the genetic architecture of migraine subtypes than was previously known.
Migraine is a fairly prevalent brain illness that affects over a billion people throughout the world. Migraine has no known aetiology, however it is thought to be a neurovascular condition involving disease mechanisms in both the brain and the blood vessels of the head.
Previous studies have found that genetic variables play a substantial role in migraine risk. However, whether the two primary migraine forms — migraine with aura and migraine without aura — share a genetic foundation has long been a point of contention.
Researchers from the International Headache Genetics Consortium put together a large genetic dataset to conduct a genome-wide association study (GWAS), seeking for genetic variations that were more common in people who experienced migraine in general or one of the two primary migraine categories.
The findings revealed that migraine subtypes share risk variables as well as risk factors that appear to be unique to each subtype. Three risk variants that appear to be specific to migraine with aura and two that appear to be specific to migraine without aura were identified in the studies.
"Our study gives the first substantial chance to assess shared and distinct genetic components in the two main migraine subtypes," said Heidi Hautakangas of the Institute for Molecular Medicine Finland, University of Helsinki, who was the paper's first author.
Furthermore, the findings backed with the theory that migraine is caused by both neuronal and vascular hereditary factors, confirming that migraine is a neurovascular condition.
Because migraine is the second leading cause of years spent disabled around the world, there is an obvious need for novel treatments.
The discovery of genetic risk areas comprising genes that encode targets for recently identified migraine-specific therapies was particularly intriguing.
Genes encoding calcitonin gene-related peptide, a protein involved in migraine attacks and blocked by the recently introduced CGRP inhibitor migraine medicines, are found in one of the newly identified areas (CALCA/CALCB). Another high-risk region includes the HTR1F gene, which codes for the serotonin 1F receptor and is a target for future migraine treatments.
"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," said Dr. Matti Pirinen, a group leader from the Institute for Molecular Medicine Finland, University of Helsinki, who led the study.
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