Migraine and Genetic Testing: What Current Tests Can and Cannot Tell You

Genetic testing has become increasingly accessible and affordable, and people with migraine who know the condition runs in their family sometimes wonder whether genetic testing can provide useful information about their diagnosis, their risk of passing migraine to their children, or their likely response to specific treatments. The honest answer is that current commercial genetic testing provides limited actionable information for most people with migraine, while the research landscape is advancing in ways that may eventually change this picture.

What We Know About the Genetics of Migraine

Migraine has a significant genetic component. Twin studies have estimated heritability at forty to sixty percent, and genome-wide association studies have identified more than forty genetic loci associated with migraine risk. The genetic architecture of common migraine is highly polygenic — influenced by many genetic variants each contributing a small amount to risk. This complexity means that current commercial genetic tests cannot reliably predict migraine risk or migraine subtype for most people.

Familial Hemiplegic Migraine and Genetic Testing

The exception is familial hemiplegic migraine, a rare autosomal dominant migraine subtype caused by mutations in specific genes including CACNA1A, ATP1A2, and SCN1A. Genetic testing is clinically meaningful for suspected familial hemiplegic migraine because identifying a causative mutation confirms the diagnosis, identifies at-risk family members, and has implications for management.

For people with typical migraine without the specific features of familial hemiplegic migraine — motor weakness during attacks, a family history of hemiplegic attacks, or other atypical features — genetic testing for these genes is unlikely to be informative.

Pharmacogenomic Testing

Pharmacogenomic testing, which evaluates genetic variants that influence drug metabolism, has more immediate clinical relevance for some people with migraine. Variants in genes including CYP2D6, CYP2C19, and CYP1A2 affect the metabolism of several medications used in migraine management, including tricyclic antidepressants and some triptans.

Direct-to-Consumer Genetic Testing

Direct-to-consumer genetic tests provide migraine susceptibility information based on genome-wide association study variants, offering a polygenic risk estimate rather than a diagnostic conclusion. People who receive a high polygenic risk score should discuss this with a healthcare provider in the context of their clinical history. People who receive a low score and have clinical symptoms consistent with migraine should not be reassured that migraine is unlikely based on the genetic result alone.

The Future of Genetic Testing in Migraine

As larger genome-wide association studies identify more genetic variants associated with migraine subtypes and treatment response, the clinical utility of genetic testing in migraine is likely to increase. Pharmacogenomic testing for treatment selection is an area of active research. For now, genetic testing is most informative in the specific clinical context of suspected familial hemiplegic migraine.