A genetic survey of patients with familial idiopathic intracranial hypertension residing in a Middle Eastern village: genetic association study

Background: The aim of this study was to determine whether genetic variants are associated with idiopathic intracranial hypertension (IIH) in a unique village where many of the IIH patients have familial ties, a homogenous population and a high prevalence of consanguinity. Several autosomal recessive disorders are common in this village and its population is considered at a high risk for genetic disorders. Methods: The samples were genotyped by the Ilumina OmniExpress-24 Kit, and analyzed by the Eagle V2.4 and DASH software package to cluster haplotypes shared between our cohort. Subsequently, we searched for specific haplotypes that were significantly associated with the patient groups. Results: Fourteen patients and 30 controls were included. Samples from 22 female participants (11 patients and 11 controls) were evaluated for haplotype clustering and genome-wide association studies (GWAS). A total of 710,000 single nucleotide polymorphisms (SNPs) were evaluated. Candidate areas positively associated with IIH included genes located on chromosomes 16, 8 (including the CA5A and BANP genes, p < 0.01), and negatively associated with genes located on chromosomes 1 and 6 (including PBX1, LMX1A, ESR1 genes, p < 0.01). Conclusions: We discovered new loci possibly associated with IIH by employing a GWAS technique to estimate the associations with haplotypes instead of specific SNPs. This method can in all probability be used in cases where there is a limited amount of samples but strong familial connections. Several loci were identified that might be strong candidates for follow-up studies in other well-phenotypes cohorts.