The following is a summary of “A cross-tissue transcriptome-wide association study reveals novel susceptibility genes for migraine,” published in the June 2024 issue of Pain by Gui et al.

Researchers conducted a retrospective study using genome-wide association studies (GWAS) to identify migraine susceptibility’s causal genes and biological underpinnings.

They utilized the FinnGen R10 dataset, which included 333,711 subjects (20,908 cases and 312,803 controls), along with the Genotype-Tissue Expression Project (GTEx) v8 EQTls files for cross-tissue transcriptome association studies (TWAS). Functional Summary-based Imputation (FUSION) validated the findings in individual tissues. Candidate susceptibility genes were identified using Gene Analysis and Multi-marker Analysis of Genomic Annotation (MAGMA). Subsequent analyses included Mendelian randomization (MR) and colocalization. Additionally, GeneMANIA analysis enhanced the understanding of the functional implications of these susceptibility genes.

The results showed that 19 susceptibility genes were identified in the cross-tissue TWAS analysis. Two new susceptibility genes, REV1 and SREBF2, were validated through single-tissue TWAS and MAGMA analysis. MR and colocalization analyses supported the findings. The REV1 may decrease migraine risk by regulating DNA damage repair, while SREBF2 may increase risk by regulating cholesterol metabolism.

Investigators concluded that the study uncovered two previously unknown genes potentially linked to migraine risk, shedding light on the genetic basis of the condition.

Source: thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01802-6