TY - JOUR
T1 - Genetic Survey of Adult-Onset Idiopathic Intracranial Hypertension
AU - Kuehn, Markus H.
AU - Mishra, Rajashree
AU - Deonovic, Benjamin E.
AU - Miller, Kimberly N.
AU - Mccormack, Shana E.
AU - Liu, Grant T.
AU - Kupersmith, Mark J.
AU - Wall, Michael
N1 - Publisher Copyright:
© North American Neuro-Ophthalmology Society.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061479028&partnerID=8YFLogxK
U2 - 10.1097/WNO.0000000000000648
DO - 10.1097/WNO.0000000000000648
M3 - Article
C2 - 29608535
AN - SCOPUS:85061479028
SN - 1070-8022
VL - 39
SP - 50
EP - 55
JO - Journal of Neuro-Ophthalmology
JF - Journal of Neuro-Ophthalmology
IS - 1
ER -