Journal of Pharmaceutical Research International

Introduction: Migraine is a chronic neurological disorder with recurrent headaches and aura, shaped by both environmental and genetic factors. In Saudi Arabia, rising prevalence contrasts with scarce genetic research. This study systematically reviews local evidence on migraine-related genetic markers and gaps.

Methodology: This systematic review and meta-analysis followed PRISMA and R-AMSTAR guidelines. An electronic literature search was performed from January 11, 2025 to April 15, 2025. We searched PubMed, Google Scholar, Embase, and MEDLINE (2005– until march 2025) for studies on Genetic Cause of Migraines in KSA. Two independent reviewers screened titles, abstracts, and full texts, with data extracted into Excel; disagreements resolved with discussion.

Results: In this systematic review and meta-analysis, 19 studies were included, of which 3 (15.8%) identified genetic associations with migraine. The pooled migraine prevalence across Saudi in the included studies was 3,643 out of 12,248 participants (39.8%, 95% CI: 28.4%–51.3%, I² = 99.6%, p < 0.001). Genetic subgroup analysis showed a higher migraine prevalence in studies reporting genetic associations (63.5%, 95% CI: 34.4%–92.7%) vs. non-genetic studies (35.6%, p = 0.0814). Family history subgroup analysis revealed significantly increased prevalence among those with a positive family history (62.0% vs. 31.5%, p = 0.0230). Gender-based analysis showed higher rates in female-dominant cohorts (49.4% vs. 32.3%, p = 0.1484). Genes associated with migraine included RETNLB, CYTB, ND5, and ATP1A2, all with risk-type associations, especially among migraine with aura cases. Three studies (15.8%) used whole-exome sequencing and validated findings through Sanger sequencing.

Conclusion: This review found that only 3 of 19 studies in Saudi Arabia investigated migraine genetics, underscoring a major research gap despite strong evidence of heritability. Limited findings suggest associations with nuclear and mitochondrial genes (RETNLB, CYTB, ND5, ATP1A2), particularly in migraine with aura, highlighting the urgent need for broader genomic research in this population.