Migraine sufferers know two things: attacks are severe (and sometimes disabling) and difficult to treat. Migraine is one of the most common chronic pain diseases worldwide, affecting up to 20% of adults.
Although recent advances have been made in the underlying biology of migraine, research is needed to uncover new therapeutic targets. Now, a large-scale international study led by deCODE Genetics (a subsidiary of Amgen) provides new insights into the biology of migraine, enables the detection of rare variants that prevent migraine, and provides novel drug targets. paved the way for the development of The results reveal several genes that influence one subtype of migraine more than others and point to new biological pathways that may be targets for the development of treatments. Masu.
This work, natural genetics In the newspaper, “Rare variants with large effects provide functional insight into the pathology of migraine with and without aura subtypes”
The group focuses on detecting sequence variants associated with migraine, combining large-scale GWAS datasets from six European populations and examining more than 1.3 million participants, 80,000 of whom We analyzed the genetic data of patients with headaches. The study included two major migraine subtypes: migraine with aura (often referred to as classic migraine) and migraine without aura.
“What makes our study unique is that it includes a large dataset from sequenced individuals. This allows for the detection of rare variants that prevent migraine and may lead to new drug targets. “This could pave the way for the development of new cancers,” said Kari Stephenson, MD, CEO of deCODE Genetics.
This study revealed associations with 44 mutations, 12 of which are novel. Four novel migraine types associated with aura (PRRT2, PALMD, ABO, and LRRK2) and 13 variants primarily associated with migraine without aura were identified.
Of particular interest are three rare mutations with large effects that indicate different pathologies underlying different types of migraine. A rare frameshift variant in the PRRT2 gene poses a significant risk for migraine with aura and another brain disease, epilepsy, but not for migraine without aura. In SCN11A, a gene known to play an important role in the sensation of pain, researchers detected several rare loss-of-function variants associated with a protective effect against migraine, but not in the same gene. A common missense variant in is associated with a moderate risk of migraine. Finally, a rare variant pointing to the KCNK5 gene confers significant protection against severe migraine and cerebral aneurysms, suggesting that a common pathway between the two diseases may be identified or that early cerebral aneurysms may be This suggests that some cases may be misclassified as migraine.
The international research team collaboration was led by scientists from Iceland’s deCODE Genetics, the Copenhagen Hospital Biobank and Danish Blood Bank studies, the Norwegian HUSK study, the US Intermountain Health study, and the data generated. It included collaborating scientists from . In a large population-based study by UK Biobank and FinnGen.