Background: Typical migraine is a heterogeneous headache disorder affecting 12% of the population and is often described as having neurovascular aetiology. Various genes and variants have been associated with non-hemiplegic migraine susceptibility, however, the exact mechanism and cause remains unknown. The first migraine and X chromosome association was made almost two decades ago and little progress has since been made in identifying an X chromosome causative variant. With this previous association and the predominance of female migraine sufferers the X chromosome remains a good candidate for further investigation.
Methodology: Here, we have employed novel paired end NGS of X chromosomal regions to sequence DNA samples from selected X-linked migraine family pedigrees available within the Genomics Research Centre. Regions sequenced included a ~4 Mb Xq12 region and the ~37 Mb region spanning Xq24 to Xq28. We have employed various bioinformatics analysis tools for the processing of the sequencing data to identify genetic variants for both the Xq12 and the Xq24-28 regions.
Results: To date, our data analysis has identified a number of variants in both X chromosomal regions examined as potential migraine candidates and we are currently validating these in the selected individuals with Sanger sequencing. Once completed, the validated sequences will be examined in additional populations to determine their association with migraine. The identification of rare functional genetic variants associated with common migraine and familial migraine, will provide a better understanding of the functional consequences of these variants and establish new candidate genes for future migraine research and the development of improved diagnostics tools.
Conclusions: Previous migraine genetic studies have improved our knowledge through uncovering factors contributing to migraine pathophysiology. This work aims to identify new markers of migraine diagnosis toward improving current treatments to relieve the burden of migraine on the population.