Migraine Triggers In The Brain
June 24, 2013

Genome Study Reveals Some Biological Migraine Triggers

redOrbit Staff & Wire Reports - Your Universe Online

Researchers have located five genetic regions that have been linked to the onset of migraines, bringing them one step closer to understanding the causes and biological triggers that underlie the debilitating headaches.

An international team of researchers conducted a large-scale genome study and identified 12 genetic regions associated with migraine susceptibility. Eight of those were located in or around genes that have a role in controlling brain circuitries, and the other two were associated with genes responsible for maintaining healthy brain tissue.

Regulating those pathways could be important to an individual’s genetic susceptibility to the recurrent throbbing headaches, which affect approximately 14 percent of all adults, the researchers said. A study detailing their findings has been published in the advanced online edition of the journal Nature Genetics.

“This study has greatly advanced our biological insight about the cause of migraine,” Dr. Aarno Palotie of the Wellcome Trust Sanger Institute said of the research.

“Migraine and epilepsy are particularly difficult neural conditions to study; between episodes the patient is basically healthy so it's extremely difficult to uncover biochemical clues,” he added. “We have proven that this is the most effective approach to study this type of neurological disorder and understand the biology that lies at the heart of it.”

The study authors discovered the susceptibilities by comparing the results of 29 different genomic studies, including more than 100,000 samples collected from both migraine patients and control samples.

They discovered that some of the regions were close to a network of genes sensitive to oxidative stress – a biochemical process that adversely affects the function of cells. Based on their findings, they believe that many of the genes at the genetic regions associated with migraines are interconnected, and that they could be causing some of the symptoms of these headaches by disrupting the internal regulation of the brain’s cells and tissues.

“We would not have made discoveries by studying smaller groups of individuals,” explained co-author Dr. Gisela Terwindt of the Leiden University Medical Centre’s Department of Neurology. “This large scale method of studying over 100,000 samples of healthy and affected people means we can tease out the genes that are important suspects and follow them up in the lab.”

In addition, the investigators managed to identify another 134 genetic regions that could be associated to migraine susceptibility with weaker statistical evidence. It is still to be determined whether or not these areas are associated with migraine susceptibility, though the authors state that other similar studies have shown that statistically weaker genetic areas could also play a role in the underlying biology of various medical conditions.

“The molecular mechanisms of migraine are poorly understood. The sequence variants uncovered through this meta-analysis could become a foothold for further studies to better understanding the pathophysiology of migraine,” explained Dr. Kári Stefánsson, President of deCODE genetics.

“This approach is the most efficient way of revealing the underlying biology of these neural disorders,” added Dr. Mark Daly of Massachusetts General Hospital. “Effective studies that give us biological or biochemical results and insights are essential if we are to fully get to grips with this debilitating condition… Pursuing these studies in even larger samples and with denser maps of biological markers will increase our power to determine the roots and triggers of this disabling disorder.”

According to the US National Institute of Neurological Disorders and Stroke (NINDS), migraines are often characterized by an intense pulsing or throbbing pain in one area of the head. They are more common amongst women than men, and they can last between four and 72 hours if left untreated.

Additional symptoms of migraines include nausea, vomiting, and sensitivity to both light and sound, and nearly one-third of those who suffer from the condition experience visual disturbances known as aura before the onset of the migraine itself. The condition has recently been recognized as the seventh disabler in the Global Burden of Disease Survey 2010, and has been estimated to be the most costly neurological disorder, the study authors added.