Scientists find genes linked to migraines

Scientists have uncovered a trio of genes tied to migraine headaches, including one in which the link is exclusive to women, according to a study published Sunday. Migraines are acutely debilitating headaches -- sometimes with an "aura", in which patients have the impression of seeing through frosted glass -- 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. The precise cause it unknown, but inheritance is thought to play a significant role. To assess the genetic component, Markus Schuerks of Brigham and Women's Hospital in Boston coordinated an international sweep of genomes in 23,230 women, 5,122 of whom suffered from migraines. So-called genome-wide association studies compare differences between individuals across the approximately three billion pairs of basic molecular building blocks found in the human genetic code. The study, published Sunday in the British journal Nature Genetics, 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. Earlier studies have shown that the same gene contains the genetic "blueprint" for a pain sensor, in both men and women. The third suspect gene, LRP1, is involved in sensing the external world and in chemical pathways inside the brain. "The brain of a person with migraine responds differently to certain stimuli, their nerve cells 'talk' differently to each other," explained Shuerks in an email. "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." None of the genetic variants appeared to be connected specifically to migraines with or without auras. 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. 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 said.