PhD Scientific Days 2022

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

The Potential Role of IGSF9B and Central Sensitization in Migraine Without Aura – a Gene Expression Study

Text of the abstract

Introduction:
Migraine is considered to be a multi-factorial neurological disorder with mild to severe influence on the quality of life, however its pathophysiology is not fully clear yet. A genome-wide association study (GWAS) found susceptibility genes indicating possible biological mechanisms in migraine. Further investigations on these hits by our gene-expression experiment may reconfirm these migraine-related findings using another approach. Furthermore, our data provides us with data regarding the change of direction, moreover it may give us more insights about migraine.

Aims:
Our aim was to compare the identified 41 GWAS genes from a large migraine population genetic study to genes that are differentially expressed in a well characterized migraine sample compared to healthy controls using RNA-Sequencing (RNA-Seq) study.

Methods:
Our study consists of 22 subjects with diagnosed episodic migraine without aura (MO), and 30 controls. Each participants provided whole blood samples which were RNA sequenced. At time-point of blood sampling subjects were headache-free and have not taken any preventive or acute medication. Our data was corrected for confounding variables age and gender and subsequently analyzed for differential expression in R. Gene was differentially expressed if nominal p values survived correction for multiple testing based on the number of risk GWAS genes in our dataset at FDR<0.05 level.
Results:
After correction for multiple testing only one significantly differentially expressed gene remained. Immunoglobulin Superfamily Member 9B (IGSF9B) was up-regulated (logFC = 0.55, FDR=0.023).

Conclusion:
In our data IGSF9B showed up-regulation and migraine was associated with a protective variant (rs561561, OR [95% CI] (0.94 [0.92–0.96]) in the original GWAS study. This gene is expressed in GABAergic interneurons affecting the function of inhibitory synapses, and thus may alter central sensitization in migraine. In conclusion, an unknown mechanism related to IGSFB9 and GABAergic interneurons can play a role in MO, however further investigations are required.

Funding:
Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002, KTIA_13_NAPA-II/14, KTIA_NAP_13-1-2013-0001, KTIA_NAP_13-2-2015-0001); 2020-4.1.1.-TKP2020; TKP2021-EGA-255; Japan Society for the Promotion of Science, P20809 (PP).