Scientists have identified for the first time three gene variations that are linked to an increased risk for migraine headache in the general population, and although there is more work to do to reveal their role, they hope the discovery will shed light on the biology of this poorly understood and debilitating condition. A report on the genome-wide association study appeared online this week in Nature Genetics.

Led by Brigham and Women’s Hospital (BWH), of Harvard Medical School in Boston, Massachusetts, the researchers identified “single-nucleotide polymorphisms” or “SNPs” in the genes PRDM16, TRPM8 and LRP1, and showed that each alters the risk for migraines by 10 to 15 percent.

“None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features,” they wrote.

SNPs (pronounced “snips”) are sequences in the DNA code where one “letter” varies. Imagine a short poem where one word is spelled differently.

Migraine affects about one in ten people worldwide, with women getting it about 3 to 4 times more often than men. It is a debilitating neurological disorder that brings a severe headache and sometimes other symptoms such as nausea and sensitivity to light and sound.

For about one third of people who get migraines, the headaches can occur with “aura”, a cluster of neurological events that includes vision disturbances such as seeing flashes or zig zag patterns, and often precede the headache phase.

Migraine’s underlying biology is somewhat of a mystery, but there are genetic factors, although their influence at the population level is also poorly understood.

The researchers found the gene variations in TRPM8, LRP1 and PRDM16 when they analyzed genetic data from women taking part in the Women’s Genome Health Study. The data covered 23,230 women including more than 5,000 who reported suffering from migraines.

They confirmed their findings by analyzing data from three independent European studies that included both men and women.

How these findings fit with current thinking about the biology of migraine make sense for two of the three discoveries. The current thinking is that migraine is an abnormality in how neurons, the cells in the brain and the nervous system, including the parts that sense and process light, pain and sound, respond to such stimuli.

For instance we already know that TRPM8 is expressed in neurons and is linked to sensing of cold and pain, and that LRP1 is expressed in cells throughout the body and is involved in a number of processes, including cell signalling in neurons.

But the potential link between PRDM16 and migraine is still a mystery: current knowledge shows that it plays a role in the generation of brown fat cells.

Lead author Dr Daniel Chasman, an Assistant Professor in the Division of Preventive Medicine at BWH and Harvard Medical School, told the press that:

“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.”

Co-lead author Dr Markus Schürks, an Instructor of Medicine in the Division of Preventive Medicine at BWH, agreed, adding that:

“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.”

Funds for the study came from a number of sources: primarily the National Institute of Neurological Disorders and Stroke, the National Heart, Lung, and Blood Institute, and the National Cancer Institute, but also from the Donald W. Reynolds Foundation, the Leducq Foundation, and the biotech giant, Amgen.

Mayo Clinic doctor, Robert Sheeler M.D., said that some lifestyle changes could help reduce migraine occurrence.

Written by: Catharine Paddock, PhD