Genome-wide association study ofHLA-DQB1*06:02negative essential hypersomnia
Open Access
- 16 April 2013
- Vol. 1, e66
- https://doi.org/10.7717/peerj.66
Abstract
Essential hypersomnia (EHS), a sleep disorder characterized by excessive daytime sleepiness, can be divided into two broad classes based on the presence or absence of the HLA-DQB1*06:02 allele. HLA-DQB1*06:02-positive EHS and narcolepsy with cataplexy are associated with the same susceptibility genes. In contrast, there are fewer studies of HLA-DQB1*06:02 negative EHS which, we hypothesized, involves a different pathophysiological pathway than does narcolepsy with cataplexy. In order to identify susceptibility genes associated with HLA-DQB1*06:02 negative EHS, we conducted a genome-wide association study (GWAS) of 125 unrelated Japanese EHS patients lacking the HLA-DQB1*06:02 allele and 562 Japanese healthy controls. A comparative study was also performed on 268 HLA-DQB1*06:02 negative Caucasian hypersomnia patients and 1761 HLA-DQB1*06:02 negative Caucasian healthy controls. We identified three SNPs that each represented a unique locus— rs16826005 (P = 1.02E-07; NCKAP5), rs11854769 (P = 6.69E-07; SPRED1), and rs10988217 (P = 3.43E-06; CRAT) that were associated with an increased risk of EHS in this Japanese population. Interestingly, rs10988217 showed a similar tendency in its association with both HLA-DQB1*06:02 negative EHS and narcolepsy with cataplexy in both Japanese and Caucasian populations. This is the first GWAS of HLA-DQB1*06:02 negative EHS, and the identification of these three new susceptibility loci should provide additional insights to the pathophysiological pathway of this condition.This publication has 66 references indexed in Scilit:
- MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypesGenetic Epidemiology, 2010
- Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studiesBioinformatics, 2010
- LocusZoom: regional visualization of genome-wide association scan resultsBioinformatics, 2010
- Genome-wide association study of bipolar disorder in European American and African American individualsMolecular Psychiatry, 2009
- Narcolepsy is strongly associated with the T-cell receptor alpha locusNature Genetics, 2009
- Genome‐wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associationsNeuropsychiatric Genetics, Part B of the American Journal of Medical Genetics (AJMG), 2008
- Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorderNature Genetics, 2008
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- A haplotype map of the human genomeNature, 2005
- Haploview: analysis and visualization of LD and haplotype mapsBioinformatics, 2004