Largest migraine genetic study to date reveals new genetic risk factors

Summary: Researchers have identified 120 regions of the genome that are linked to migraine risk.

Source: University of Helsinki

An international consortium of leading migraine scientists has identified more than 120 regions of the genome that are linked to migraine risk.

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

In the largest migraine genome study to date, researchers more than tripled the number of known genetic risk factors for migraine. Of the 123 genetic regions identified, two contain recently developed migraine-specific drug target genes.

The study involved 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 suffered from migraine.

The new results, published on February 3, 2022 in the journal Natural geneticsalso uncovered more of the genetic architecture of migraine subtypes than previously known.

Neurovascular mechanisms underlie the pathophysiology of migraine

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

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

To better understand specific risk genes, researchers from the International Headache Genetics Consortium gathered a large set of genetic data to conduct a genome-wide association study (GWAS), looking for more genetic variants. common in people with migraine in general, or one of the two main types of migraine.

The results demonstrated that migraine subtypes have both common risk factors and risk factors that appear to be subtype-specific. Analyzes revealed three risk variants that appear specific to migraine with aura and two that appear specific to migraine without aura.

“In addition to implicating dozens of novel regions of the genome for more targeted investigation, our study offers the first significant opportunity to assess shared and distinct genetic components in the two major subtypes of migraine,” said the former. study author, Heidi Hautakangas of the Finnish Institute of Molecular Medicine, University of Helsinki.

Additionally, the results supported the concept that migraine is caused by both neural and vascular genetic factors, reinforcing the idea that migraine is truly a neurovascular disorder.

Potential to point to new migraine therapies

As migraine is the second largest contributor to years lived with disability worldwide, there is clearly a significant need for new treatments.

Migraine is a very common brain disorder with over a billion patients worldwide. Image is in public domain

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

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

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Dr Matti Pirinen, group leader of the Institute of Molecular Medicine of Finland, University of Helsinki, who led the study, said that “these two new associations close to genes already targeted by effective migraine drugs suggest that there may be other potential drugs. targets among new genomic regions, and provide a clear rationale for future genetic studies with even larger sample sizes.

About this genetics and migraine research news

Author: Press office
Source: University of Helsinki
Contact: Press office – University of Helsinki
Picture: Image is in public domain

Original research: Free access.
“Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles” by Matti Pirinen et al. Natural genetics


Abstract

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Migraine affects more than a billion people worldwide, but its genetic basis remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, 86 of which were previously unknown. These loci provide the opportunity to assess shared and distinct genetic components in the two major subtypes of migraine: migraine with aura and migraine without aura.

Risk locus stratification using 29,679 cases with subtype information indicated three risk variants that appear specific to migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific to migraine without aura (close to SPINK2 and near FECH) and nine that increase susceptibility to migraine regardless of subtype. Novel risk loci include genes encoding recent migraine-specific drug targets, namely the calcitonin gene-related peptide (CALCA/CALCB) and the serotonin 1F receptor (HTR1F).

Overall, genomic annotations among migraine-associated variants were enriched across vascular and central nervous system tissue/cell types, unequivocally supporting that neurovascular mechanisms underlie migraine pathophysiology.

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