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Genetic Survey of Adult-Onset Idiopathic Intracranial Hypertension

Kuehn, Markus H., PhD; Mishra, Rajashree, BS; Deonovic, Benjamin E., MS; Miller, Kimberly N., BA; McCormack, Shana E., MD; Liu, Grant T., MD; Kupersmith, Mark J., MD; Wall, Michael, MD the NORDIC IIHTT Study Group

doi: 10.1097/WNO.0000000000000648
Original Contribution: PDF Only

Background: Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure of unknown cause. IIH has been shown to be associated with female sex as well as obesity. This genome-wide association study was performed to determine whether genetic variants are associated with this condition.

Methods: We analyzed the chromosomal DNA of 95 patients with IIH enrolled in the Idiopathic Intracranial Hypertension Treatment Trial and 95 controls matched on sex, body mass index, and self-reported ethnicity. The samples were genotyped using Illumina Infinium HumanCoreExome v1-0 array and analyzed using a generalized linear mixed model that accounted for population stratification using multidimensional scaling.

Results: A total of 301,908 single nucleotide polymorphisms (SNPs) were evaluated. The strongest associations observed were for rs2234671 on chromosome 2 (P = 4.93 × 10−07), rs79642714 on chromosome 6 (P = 2.12 × 10−07), and rs200288366 on chromosome 12 (P = 6.23 × 10−07). In addition, 3 candidate regions marked by multiple associated SNPs were identified on chromosome 5, 13, and 14.

Conclusions: This is the first study to investigate the genetics of IIH in a rigorously characterized cohort. The study was limited by its modest size and thus would have only been able to demonstrate highly significant association on a genome-wide scale for relatively common alleles exerting large effects. However, several variants and loci were identified that might be strong candidates for follow-up studies in other well-phenotyped cohorts.

Department of Ophthalmology and Visual Sciences (MHK, KNM, MW), The University of Iowa, Iowa City, Iowa; Division of Human Genetics (RM), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Biostatistics (BED), The University of Iowa, Iowa City, Iowa; Division of Endocrinology and Diabetes (SEM), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pediatrics (SEM), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Ophthalmology (GTL), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and New York Eye and Ear Infirmary (MJK), Icahn School of Medicine at Mount Sinai, New York, New York.

Address correspondence to Markus H. Kuehn, PhD, Department of Ophthalmology and Visual Sciences, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242; E-mail:

Supported by U10 EY017281-01A1, U10 EY017387-01A1, 3U10EY017281-01A1S1.

The authors report no conflicts of interest.

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© 2019 by North American Neuro-Ophthalmology Society