Whole-exome sequencing reveals migraine associated novel functional variants

Background Migraine, as the 7th most disabling neurological multi-symptomatic disease condition and 26.9% prevalence in Saudi females lacks studies on SNPs for their relation with migraine aura. Methods This study was conducted on 40 Arab ancestry young female subjects, among whom 50% cases with migraine and remaining controls were used to identify the migraine associated novels genes and risk variants. After quality controls, 3365343 missense, frameshift, missense splice region variants and insertion-deletion (indels) polymorphisms were tested for association to migraine. Results Seventeen significant (p value 9.091×10− 05) functional variants in 12 genes (RETNLB, SCAI, ADH4, ESPL1, CPT2, FLG, PPP4R1, SERPINB5, ZNF66, ETAA1, EXO1 and CPA6) were migraine risk associated including a stop gained frameshift (-13-14*SX) variant in the gene RETNLB (rs5851607; p value 3.446×10− 06). Gene analysis revealed that half of the significant novel migraine risk genes expressed in temporal lobe (p-value 0.0058) of the cerebral cortex. Conclusions This first study in female (22.10 ± 3.63 years) migrainers is the first one exploring migraine risk variants in Arab ancestry.