Scientists Identify Genes Linked to Migraines

Inheriting any one of 3 gene variants raises risk for severe headaches by up to 15%, researchers say.

Researchers have identified three genes linked to migraine headache and found that people who inherit any one of these genes have a 10 to 15 percent greater risk for the condition.

Migraine headache -- an abnormality in the response of nerve cells to stimuli -- is characterized by recurring severe headaches, which often result in nausea as well as sensitivity to light and sound.In examining genetic data from more than 23,000 women, including over 5,000 migraine sufferers, the researchers found an association between the headaches and variations in three genes: TRPM8 (which plays a role in sensitivity to cold and pain), LRP1 (a gene involved in the transmission of signals between neurons) and PRDM16.

"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," the study's lead author, Dr. Daniel Chasman, assistant professor in the preventive medicine division at Brigham and Women's Hospital and Harvard Medical School, said in a hospital news release.

One migraine expert called the findings "very exciting." "The thinking for a long time was that migraine is most commonly a multi-genetic condition with potentially many genetic variations that contribute," noted Dr. Audrey Halpern, clinical assistant professor in the department of neurology at NYU Langone Medical Center in New York City. "We clearly understand now that migraine is a condition characterized by disordered sensory processing."Although the study authors said the findings are encouraging, they noted that more research is needed to better understand exactly how each of these three genes is associated with migraine.Halpern agreed that much more study lies ahead to unravel the genetics of migraine. "This current research will help us more fully understand what happens during migraine, but there is also much more to learn," she said. "We've always known it's a genetic condition -- but the last 10 years we've learned it's a neurological condition. This study brings those two ideas together."

The report is published in the June 12 online edition of the journal Nature Genetics.

SOURCES: Audrey Halpern, M.D., clinical assistant professor, department of neurology, NYU Langone Medical Center, New York City; Brigham and Women's Hospital.

Investigation of TNFA 308G > A and TNFB 252G > A polymorphisms in genetic susceptibility to migraine.

J Neurol. 2009 Dec 25; Ghosh J, Joshi G, Pradhan S, Mittal B look for the association of tumor necrosis factor (TNF) gene polymorphisms (TNFA 308G > A, and TNFB 252G > A) in genetic susceptibility to migraine. The pathogenesis of migraine involves many immune-mediated mechanisms in the vascular endothelium. TNF, being a potent immunomodulator and pro-inflammatory cytokine, is suggested to be involved in inflammatory reactions leading to migraine attacks. A total of 216 normotensive migraine patients, 160 tension type headache (TTH) patients and 216 healthy controls (HC) were recruited in the study. The genetic polymorphisms were investigated through SNP association analysis using a matched case control migraine population. Genotyping of TNFA 308G > A polymorphism and TNFB 252G > A was done using ARMS PCR and PCR-RFLP, respectively. A borderline association was observed in TNFA 308GA genotype in migraine patients versus HC (p = 0.043; OR = 1.763; 95% CI = 1.019-3.051). After sub-grouping migraine into migraine with aura (MA) or without aura, significant difference at genotypic (p = 0.015; OR = 2.293; 95% CI = 1.172-4.487) as well as allelic (p = 0.035; OR = 1.955; 95% CI = 1.047-3.651) level was evident. The difference was even more significant in female MA at genotypic (p = 0.006; OR = 2.901; 95% CI = 1.361-6.181) and allelic level (p = 0.017; OR = 2.318; 95% CI = 1.159-4.635) as well as for A allele carriers in MA [p value = 0.020; OR = 2.205 (1.132-4.295)] and female MA (p value = 0.008; OR = 2.741; CI = 1.297-5.792). No association of TNFB252G > A was observed in migraine patients or any subgroups. We did not find any association of TNFA or TNFB gene polymorphisms with TTH. In conclusion, the TNFA 308G > A polymorphism was found to be associated with MA, particularly in females, whereas we could not find any association of TNFB 252G > A polymorphism in genetic susceptibility to migraine on comparing the migraine patients with HC or TTH patients.