What Causes Migraines? According to Research, It’s All in the Genetics

Are Migraines Genetic?

Are Migraines Genetic?A migraine is often seen running in families from clinical practice and is confirmed in formal scientific studies.

Take me for example. Migraines go back at least three generations on my mother’s side of the family. My grandfather, mother, aunt, cousins and myself all have or had a migraine.

A migraine is a complex genetic disorder where genes, environment, stress and hormonal changes interact together.

These types of disorders are hard to understand because of how complex they are.

What makes it hard is many genes are combining in different ways in different people. Picking out the genes responsible for a migraine then becomes like picking out a needle in a haystack.

Familial Hemiplegic Migraine (FHM)

By looking at the DNA of large families where a migraine is passed down every generation, it is possible to find these genes.

One example of this is with familial hemiplegic migraine. Four genes have been identified with familial hemiplegic migraine:

  • ATP1A2
  • SCN1A
  • PRRT2

These four genes have been found to cause a familial hemiplegic migraine.

Researchers believe that mutations in the first three genes can upset the balance of ions in neurons and disrupt the regular release and uptake of certain neurotransmitters in the brain.

Mutations in the PRRT2 genes, although the mechanism is unknown, is also speculated to disrupt normal control of neurotransmitter release. The changes in signaling between neurons because of these mutations lead people with familial hemiplegic migraine to develop severe headaches.

ATPase Na+/K+ Transporting Subunit Alpha 2 (ATP1A2) Gene

The ATP1A2 gene provides instructions for making one part (the alpha-2 subunit) of a protein known as a Na+/K+ ATPase.


This protein uses energy from a molecule called adenosine triphosphate (ATP) to transport charged atoms (ions) into and out of cells. Specifically, it pumps sodium ions (Na+) out of cells and potassium ions (K+) into cells.

Calcium Voltage-Gated Channel Alpha Subunit 1 (CACNA1A) Gene

The CACNA1A gene provides instructions for making one part (the alpha-1 subunit) of a calcium channel called CaV2.1. This subunit forms the hole (pore) through which calcium ions can flow.

CaV2.1 channels play an essential role in communication between nerve cells (neurons) in the brain.

These channels help control the release of neurotransmitters, which are chemicals that relay signals from one neuron to another. Researchers believe that CaV2.1 channels are also involved in the survival of neurons and the ability of these cells to change and adapt over time.

Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) Gene

The SCN1A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.1. These channels are found in the brain and muscles, where they control the flow of sodium ions into cells.

In the brain, NaV1.1 channels are involved in transmitting signals from one neuron to another.

Communication between neurons depends on chemicals called neurotransmitters, which are released from one neuron and taken up by neighboring neurons. The flow of sodium ions through NaV1.1 channels helps determine when neurotransmitters will be released.

Proline Rich Transmembrane Protein 2 (PRRT2) Gene

The PRRT2 gene provides instructions for making the proline-rich transmembrane protein 2. The function of this protein is unknown, although it is thought to be involved in signaling in the brain.

Studies show that it interacts with another protein called SNAP25, which participates in signaling between neurons in the brain. SNAP25 helps control the release of neurotransmitters, which are chemicals that relay signals from one neuron to another.

Next page: Other genes that may influence migraines and actionable steps to take to diagnosis and identify gene mutations.

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