Migraine, as the seventh most disabling neurological disease with 26.9% prevalence in Saudi females, lacks studies on identifying associated genes and pathways with migraines in the Arab population. This case control study aims to identify the migraine-associated novel genes and risk variants. More than 1900 Arab ancestry young female college students were screened: 103 fulfilled the ICHD-3 criteria for migraine and 20 cases confirmed in the neurology clinic were included for the study with age-matched healthy controls. DNA from blood samples were subjected to paired-end whole-exome sequencing. After quality control, 3365343 missense, frameshift, missense splice region variants and insertion–deletion (indels) polymorphisms were tested for association with migraine. Significant variants were validated using Sanger sequencing. A total of 17 (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 associated with higher migraine risk, 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 were expressed in the temporal lobe (p-value 0.0058) of the cerebral cortex. This is the first study exploring the migraine risk of 17 functional variants in 12 genes among Saudi female migraineurs of Arab ancestry using whole-exome sequencing. Half of the significant genes were expressed in the temporal lobe, which expands migraine pathophysiology and early identification using biomarkers for research possibilities on personalised genetics.

Background: Pediatric polypharmacy is increasingly recognized among children with chronic medical conditions; however, data from outpatient settings, particularly in the Middle East, remain limited. This study aimed to determine the prevalence, patterns, and factors associated with pediatric polypharmacy among outpatients at a tertiary care hospital. Methods: We conducted a retrospective cross-sectional study of pediatric outpatients (<18 years) with at least one recorded prescription attending a tertiary hospital between October 2024 and October 2025. Polypharmacy was defined as the concurrent use of five or more eligible prescribed medications for at least 30 consecutive days. Oral, inhaled, and injectable medications were included, whereas PRN, topical, ophthalmic, otic, intranasal, and routine nutritional supplements were excluded. Therapeutic folic acid, iron, calcium supplements, and pyridoxine were retained when prescribed for specific clinical indications. Descriptive statistics, univariable analyses, Spearman correlation, and multivariable logistic regression were performed. Results: Among 6578 pediatric outpatients, 82 met the study definition of polypharmacy, yielding a prevalence of 1.2% (95% CI: 1.01–1.54%). Children with polypharmacy were significantly older and had greater outpatient, inpatient, emergency department, and total healthcare utilization than those without polypharmacy. Multivariable logistic regression identified older age (OR 1.136, 95% CI 1.076–1.199; p < 0.001) and outpatient visit frequency (OR 1.350, 95% CI 1.288–1.417; p < 0.001) as factors independently associated with polypharmacy, whereas sex, inpatient visits, and emergency visits were not independently associated. Epilepsy was the most common diagnosis, followed by bronchial asthma and chronic kidney disease. Pantoprazole was the most frequently prescribed medication, while endocrinology and rheumatology were the most frequently attended specialties. Conclusions: Using a definition requiring sustained concurrent medication use, pediatric polypharmacy was uncommon in this outpatient population but was independently associated with older age and greater outpatient healthcare utilization. These findings support targeted medication review and optimization strategies for children with chronic diseases requiring frequent outpatient follow-up and provide baseline data for pediatric medication safety initiatives.