Genome-Wide Association Study of Idiopathic Intracranial Hypertension in the All of Us National Data Repository
Sofia Zoullas1, Stephen Richards4, Anthony J. Griswold2, Liza Smirnoff3
1University of Miami Miller School of Medicine, 2John P. Hussman Institute for Human Genomics, 3University of Miami Department of Neurology, University of Miami Miller School of Medicine, 4Human Genome Sequencing Center, Baylor College of Medicine
Objective:
Identify potential genetic factors influencing idiopathic intracranial hypertension (IIH) pathogenesis within the All of Us (AoU) database and using the All by All (AxA) tables.
Background:
Prior research has revealed instances of familial aggregation of IIH, suggesting a genetic influence in disease etiology.
Design/Methods:
We identified a cohort of individuals ages 18 and older via ICD 9/10 codes for IIH. We excluded subjects with common risk factors for hydrocephalus. We are performing a GWAS to identify potential associated genetic alleles using available genome sequence data and standard methods using the AoU workbench. In tandem, we surveyed AxA for our phenotype of interest to assess cohort demographics and any pertinent genetic findings to compare to our curated cohort. The AxA tables were created by AoU as a large genetic association result database using short-read whole genome sequence (srWGS) and phenotypic data collected from the platform for researchers to access results directly for ~3,400 phenotypes.
Results:
Our cohort comprises 597 subjects the majority of whom are White females aged 18-44; the AxA cohort comprises 735 subjects who are also majority females aged 18-44 with European ancestry. We found two alleles with p-values <5e10-8 of uncertain biological significance through the AxA dataset. Our gene-based analysis identified 11 associations of marginal statistical significance; we are investigating genes with a p-value of <2.5e10-5.
Conclusions:
Our demographic results are consistent with previously described epidemiology in both our cohort and the AxA cohort: premenopausal females of European ancestry who suffer from comorbid obesity. Interpretation of AxA results is underway and expected to be completed by December 2024, along with the GWAS using our curated cohort. Through improving the quality of our IIH cohort by removing confounders, we aim to increase confidence and power in the results, and help elucidate our AxA findings.
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