The world’s largest study of migraines has discovered dozens of new genetic regions linked to their onset, opening new doors to understanding what causes the debilitating headaches.
The international study published in Nature Genetics, jointly-led by QUT’s Associate Professor Dale Nyholt, from the Institute of Health and Biomedical Innovation (IHBI), said the research helped to greatly advance the biological understanding of what caused migraines.
“Migraine is a difficult condition to study because between episodes the patient is basically healthy, so it’s extremely hard to uncover biological or biochemical clues,” Professor Nyholt said.
“But these sorts of biological results and insights are essential if we are to fully get to grips with this debilitating condition.”
Researchers identified 44 independent DNA variants robustly associated with migraine risk that mapped to 38 distinct genes (or genomic loci), including 28 not previously reported.
Professor Nyholt said rather than migraine being the result of brain dysfunction with secondary vascular changes, the findings indicated vascular dysfunction, or poor blood vessel function, is a primary mechanism underlying migraine.
“Typically throbbing in nature, and accompanied by aura, nausea, vomiting, light and noise sensitivity, migraine is the third most common disease worldwide,” he said.
The large international study, co-led by Professor Aarno Palotie and colleagues at the Broad Institute USA, compared eight million DNA variants between 60,000 migraine patients and 316,000 controls drawn from 22 different genomic studies.
“The identification of these genetic factors is the first crucial step to uncover the biological pathways of migraine,” Professor Nyholt said.
“This is important, because there is a long-running debate about whether migraine is a disease of vascular dysfunction, or a result of brain dysfunction with secondary vascular changes.
“Hence, our results are important given they provide strong genomic support for vascular dysfunction as a primary mechanism underlying migraine.”
He said the identified genomic regions had provided important insight into migraine to show enrichment for genes expressed in vascular and smooth muscle tissues.
“Although it remains likely that neurogenic mechanisms are also involved in migraine, the vascular finding is consistent with known comorbidities and previously reported shared genetic risk among migraine, stroke, and cardiovascular diseases.”
Professor Nyholt said migraine—characterized by recurrent attacks of disabling headache—is the third most common disease worldwide, with a lifetime prevalence of between 15 and 20 per cent.
“In terms of years of life lost to disability, migraine ranks as the seventh most disabling of all diseases worldwide, and is the third most costly neurological disorder after dementia and stroke," he said.
“Despite this large impact, the exact causes of migraine are unknown and there are no recognisable, diagnostic, pathological changes.
“However, twin and family studies indicate that migraine has a significant genetic component.”
Professor Nyholt said through the discovery of novel pathways and new targets for drug therapy, the research provided a deeper understanding of migraine and would ultimately improve the ability to prevent and treat attacks.
This study is published in Nature Genetics and can be viewed at http://www.nature.com/ng/journal/vaop/ncurrent/index.html
or http://dx.doi.org/10.1038/ng.3598 and may be cited using the digital object identifier (DOI), doi:10.1038/ng.3598
Media contact: Rose Trapnell, rose.trapnell@qut.edu.au, 07 3138 2361 or 0407 585 901
