Genetic link to migraine found

By Dr. Ananya Mandal, MDJun 13 2011

In a latest study researchers have discovered a trio of genes tied to migraine headaches, including one in which the link is exclusive to women.

Migraines are acutely debilitating headaches that strike up to 20 percent of the population. Scientists describe the condition, which is three to four times more common in women, as a brain disorder in which neurons, or brain cells, respond abnormally to stimuli like light and sound. Migraines rank in the World Health Organization’s top 20 most disabling lifetime illnesses. Victims feel very sick and cannot tolerate light or noise. An attack can last days and strike an average of 13 times a year, costing the economy £2billion a year in days off and NHS care. The precise cause is unknown, but inheritance is thought to play a significant role.

For this study Markus Schuerks of Brigham and Women's Hospital in Boston coordinated an international study of genomes in 23,230 women, 5,122 of whom suffered from migraines. The team compared differences across the approximately three billion pairs of basic molecular building blocks found in the human genetic code in the women.

The study was published Sunday in the British journal Nature Genetics and is the largest to date of its kind. It found variations in three genes that showed up more frequently in migraine patients. Two of them, known as PRDM16 and TRPM8, were specific to migraines, as opposed to other kinds of headaches. TRPM8, in addition, was linked to migraines only in women. The third suspect gene, LRP1, is involved in sensing the external world and in chemical pathways inside the brain.

Shuerks explained, “The brain of a person with migraine responds differently to certain stimuli, their nerve cells 'talk' differently to each other…Many neurotransmitters are involved in this cross-talk and some seem to have a special role in migraines. LRP1 interacts with some of these neurotransmitter pathways and may thus modulate nerve responses that promote or suppress migraine attacks.”

The findings, published in Nature Genetics, were replicated in two smaller population-based studies, one in the Netherlands and the other in Germany, and in a clinical group followed by the International Headache Genetics Consortium.

“Inheritance of any of the genetic variants alters migraine risk by about 10 to 15 percent,” said Schuerks. This he said that the influence of these genes is probably not large enough to be immediately used as a diagnostic tool. But the result “is an advancement of the understanding of migraine biology,” he added.