Whole-exome sequencing reveals migraine associated novel functional variants

Abstract

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.

Whole-Exome Sequencing Reveals Migraine-Associated Novel Functional Variants in Arab Ancestry Females: A Pilot Study

“…Gene analysis revealed that 6 of the significant 12 novel migraine risk genes were expressed in the temporal lobe of the cerebral cortex. The present study adds a molecular insight into the observations on the temporal lobe [ 29 ] and migraine-associated genes [ 30 , 31 ] and opens new avenues for migraine research. The current study will help in power calculations in the future and will provide potential loci to look for in replication studies.…”