BWH Researchers Identify Gene Variation Linked to Migraines

BWH Researchers Identify Gene Variation Linked to Migraines

Boston, MA - Researchers from Brigham and Women's Hospital (BWH) have, for the first time, identified three genes, in which genetic variation is associated with an increased risk for migraine headache at the population level. They found that inheritance of any of the three genetic variants altered risk for migraines by 10 - 15 percent. The findings appear on-line in the journal Nature Genetics June 12, 2011.

Analyzing the genetic data from 23,230 women who are participants in the Women's Genome Health Study, more than 5,000 of whom reported suffering from migraine headaches, the researchers identified associations of genetic variation in TRPM8, LRP1 and PRDM16. The genetic associations were confirmed by analyzing genetic data from three independent European studies of both men and women. The gene TRPM8 is expressed in neurons where previous research has focused on its role in sensitivity to cold temperatures and pain. LRP1 is expressed throughout the body. In the nervous system, it has been shown to interact with other proteins that modulate transmission of signals between neurons.

Migraines are characterized by recurring, severe headaches and include additional symptoms such as nausea as well as sensitivity to light and sound. Migraines affect women 3 - 4 times more often than men. 

Current thinking views migraine as an abnormality in the response of neurons to stimuli. Supporting this thinking, the association at TRPM8 is consistent with its role in the sensation of pain and cold while the association at LRP1 fits with its role in neuronal signaling. The potential connection between PRDM16 and migraine remains unknown.

"While migraine remains incompletely understood and its underlying causes difficult to pin down, identifying these three genetic variants helps shed light on the biological roots for this common and debilitating condition," said Dr. Daniel Chasman, lead author of the study and an Assistant Professor in the Division of Preventive Medicine at BWH and Harvard Medical School.

Co-lead author Dr. Markus Schürks, an Instructor of Medicine in the Division of Preventive Medicine at BWH, added, "We are very encouraged with the findings of this study and how they lend to advancement in understanding the causes of migraine, but to fully understand the precise contribution of all three genes will require more research."

The research was funded by the National Institute of Neurological Disorders and Stroke, the National Heart, Lung, and Blood Institute, and the National Cancer Institute. Further support for part of the research came from the Donald W. Reynolds Foundation, the Leducq Foundation, and Amgen. Other senior investigators from Brigham and Women's Hospital were Tobias Kurth, Julie Buring, Paul Ridker, and Robert Zee. Other participating researchers are European collaborators from the University of Leiden in the Netherlands, the University of Greifswald in Germany, and members of the International Headache Genetics Consortium led by the Sanger Institute in the United Kingdom.