Studying migraine and genetics
By: Katherine Markel, UCL Genetics Institute
My name is Katherine Markel and I’m a recent graduate from University College London (UCL)’s Genetics of Human Disease MSc programme. I’m also a recipient of The Migraine Trust’s Susan Haydon Bursary, which supported research I undertook for my dissertation on genetic variants in UK Biobank participants who experience migraine attacks. UK Biobank is a biomedical database containing genetic and health information from half a million people in the UK. My project was supervised by Professor David Curtis of the UCL Genetics Institute, whose previous work studying hypertension (high blood pressure), diabetes, and hyperlipidaemia (high levels of fat in the blood) in UK Biobank participants formed the basis of this study.
Migraine is one of the most common and debilitating neurological conditions worldwide, with a well-documented tendency to run in families, suggesting an inherited genetic component to its development. Still, relatively little is known about the genetic mechanisms that contribute to migraine. Since genes are the instructions for making proteins, variants in genes can lead to changes in proteins made in the body. This, in turn, can alter the functionality of certain proteins and contribute to the development of disease. Much of what we know about the molecular mechanisms of migraine has been the result of identifying and studying the impact of variants in specific genes that cause rare subtypes of migraine. However, several other genes have been linked to different conditions which commonly present with migraine, sometimes decades before other signs and symptoms appear.
Do variants in these genes contribute to a higher risk of developing the more common forms of migraine?
To help answer this question, we selected 10 genes associated with migraine and performed analyses to determine if damaging variants in these genes were more common in UK Biobank participants who lived with migraine compared to those who did not. We also performed additional investigations into specific variants identified in the literature in those 10 genes, including a particular variant in a gene that encodes the TRESK protein which was identified in a multigeneration family who lived with migraine with aura.
The results of our study indicate that none of the 10 genes made UK Biobank participants more susceptible to developing the more common forms of migraine. Furthermore, none of the specific variants we identified from the literature were significantly more common in those who have migraine compared to those who do not, including the TRESK variant previously identified in familial migraine with aura.
These findings cast doubt on the causal role that variants in these genes play in the development of the more common forms of migraine. They also lend support to the theory that the molecular mechanisms that underlie rare monogenic (controlled by a single gene) forms of migraine are different than those of the more common forms of the disease. Since there are finite resources available to study migraine and time is of the essence to develop new treatments for those who live with the condition, our findings could be used to steer those resources in a timely fashion to more promising targets.
To read the full study for yourself, please visit https://doi.org/10.1101/2021.12.02.21267184.
Author’s note: I would like to offer my sincere thanks to The Migraine Trust for helping fund this research, to Professor David Curtis who provided the methodology and programs we modified to conduct this study, to the staff who operate and maintain UCL’s High Performance Computing Cluster, and to my mother for her tireless support.
Learn more about migraine and genetics here.