genetics

The Genetics of Migraine

In the United States, 28 million individuals have migraine, but more than half of those living with migraine go undiagnosed by a health care provider. In an effort to create better diagnosis tools and treatment options for patients with migraine, a team of researchers are investigating the genetic factors behind migraine.

The research, led by William Renthal, MD, PhD, was recently published in Headache: The Journal of Head and Face Pain and was presented at the 61st Annual Scientific Meeting of the American Headache Society.1

William Renthal, MD, PhD, is the director of Headache Genetics at the John R. Graham Headache Center at Brigham and Women’s Faulkner Hospital in Boston, Massachusetts. He is also an instructor of neurobiology at Harvard Medical School in Boston, Massachusetts.

We caught up with Dr Renthal after his presentation.

CONSULTANT360: Can you tell us more about your research and what you found?

William Renthal: Migraine is a genetic disorder caused by genetic variation scattered across dozens of genes and regions of DNA that regulate how much a gene is expressed. While we know this genetic variation is associated with migraine, we have no idea how to understand how they might be contributing to migraine pathophysiology. My research focuses on identifying the nervous system cell types in which putative migraine-associated genes are expressed. This is a critical next step in order to study the mechanisms by which each genetic variant contributes to migraine susceptibility and hopefully identify fundamentally new approaches for treating migraine. 

C360: How did this research come about?

WR: The nervous system is made up of hundreds, if not thousands, of distinct cell types, so it is critical to understand where genes are expressed in order to begin to study their biological function—especially in a disease as heterogeneous as migraine. About 3 years ago, a new high-throughput technology was developed here at Harvard to characterize the genes that are expressed within individual cells. This opened the door for the first time to study where putative migraine-associated genes are expressed in human nervous tissues involved in migraine pathophysiology.

C360: How might your findings impact clinical practice or the future of migraine medicine?

WR: Once we identify the nervous system cell types in which migraine-associated genes are expressed, our goal is to develop a simple saliva test to understand the cell types that are likely contributing to an individual's migraine susceptibility. By grouping patients based on their underlying pathophysiology rather than headache descriptions, I believe we will be able to conduct better clinical trials and more quickly guide patients to the most effective therapy. 

C360: What is the next step in your research?

WR: A key next step is to complete our single-cell atlas of human trigeminal ganglia, one of the key nervous system tissues involved in migraine. We are really close!

C360: What is the key take-home message for neurologists?

WR: Neurologists are known for localizing structural lesions in the nervous system. Single-cell genomics now enables us to rapidly localize genetic lesions to the correct nervous system cell type. My research leverages this technology to develop new diagnostic and treatment options for patients with migraine.  

 

Reference:

  1. Renthal W. Single-cell RNA sequencing of migraine associated genes across neuronal, glial and neurovascular cell types in the central and peripheral nervous system. Paper presented at: American Headache Society 61st Annual Scientific Meeting; July 11-14, 2019: Philadelphia, PA. 

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