FINAL REPORT: Genomics of Migraine from the CHAMP study: DNA Polymorphism Identification

Summary

The Children and Adolescent Migraine Prevention Study (CHAMP) was designed to determine an effective way to prevent migraine in children and adolescents. The results of the CHAMP study demonstrated the equal effectiveness of amitriptyline, topiramate and placebo in up to 70% of children and adolescents. Migraine is known to have a significant inheritance pattern, and an international collaborative has identified up to 38 gene polymorphisms (variations in individual genes) associated with migraine in adults. The CHAMP study provided a well characterized group of participants (360) with the potential of genetic influences. Blood was collected from these participants and their DNA was isolated. A subset of these samples (60 participants) were identified to compare the best responders with the lowest responders. These samples were analyzed using Whole Exome Sequencing so that the known polymorphisms could be analyzed, and the resulting dataset would be available if additional genes were identified in the future. The mRNA expression patterns for these same participants were also determined and will be available for comparison to the polymorphisms and pathways identified in this study. From these samples, we found that 2 of the 38 polymorphisms identified as being associated with migraine in adults were also common in the children and adolescent participants while 36 were not.

Hypothesis vs. Findings

Our general hypothesis is that the genetic nature of migraine will serve as a foundation for further detailed characterization, sub-group identification and treatment response. This study focused on identifying whether previously identified polymorphisms also occurred within the CHAMP study population to gain further insights from this identification. The results demonstrated that 2 of the gene changes identified as different from the normal population were very common in the CHAMP population. In other words, they were very common in the children and adolescents with migraine. The remaining 36 polymorphisms were not different from the general population. Further exploratory analysis has demonstrated additional genetic polymorphisms outside the 38 originally screened that appear to identify specific response patterns to individual treatment.

Unanswered Questions

As the entire CHAMP study sample (360 participants with potential DNA to analyzed) is yet to be screened, further confirmation of these findings is still needed, as well as potentially identifying the presence of a lower frequency of the remaining polymorphisms. Additionally, the hypothesis that treatment response can be predicted needs to be confirmed.

What this Research Means to You

This research confirms our hypothesis that previously identified genetic polymorphisms for adults are also a contributor to migraine in children and adolescents. The dataset generated will provide a foundation for further analysis, including refining genetic patterns that predict response and guiding our understanding of the molecular biological pathophysiological basis for migraine, not only in children, but also in adults.