Abstract | BACKGROUND: METHODS: We tested for genome-wide and candidate gene associations in 42 narcolepsy cases and 4981 controls. Genotyping was performed on Illumina arrays, HLA alleles were imputed using SNP2HLA, and single nucleotide polymorphisms were imputed using the haplotype reference consortium panel. The genome-wide significance threshold was p < 5 × 10-8, and the nominal threshold was p < 0.05. Results were replicated in 32 cases and 7125 controls. Chromatin data was used for functional annotation. FINDINGS: Carrying HLA-DQB1*06:02 was significantly associated with narcolepsy, odds ratio (OR) 39.4 [95% confidence interval (CI) 11.3, 137], p = 7.9 × 10-9. After adjustment for HLA, GDNF-AS1 (rs62360233) was significantly associated, OR = 8.7 [95% CI 4.2, 17.5], p = 2.6 × 10-9, and this was replicated, OR = 3.4 [95% CI 1.2-9.6], p = 0.022. Functional analysis revealed variants in high LD with rs62360233 that might explain the detected association. The candidate immune-gene locus TRAJ (rs1154155) was nominally associated in both the discovery and replication cohorts, meta-analysis OR = 2.0 [95% CI 1.4, 2.8], p = 0.0002. INTERPRETATION:
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Authors | Pär Hallberg, Hans Smedje, Niclas Eriksson, Hugo Kohnke, Makrina Daniilidou, Inger Öhman, Qun-Ying Yue, Marco Cavalli, Claes Wadelius, Patrik K E Magnusson, Anne-Marie Landtblom, Mia Wadelius, Swedegene |
Journal | EBioMedicine
(EBioMedicine)
Vol. 40
Pg. 595-604
(Feb 2019)
ISSN: 2352-3964 [Electronic] Netherlands |
PMID | 30711515
(Publication Type: Journal Article)
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Copyright | Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Biomarkers
- HLA Antigens
- Influenza Vaccines
- pandemrix
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Topics |
- Adolescent
- Adult
- Alleles
- Biomarkers
- Cell Survival
(genetics, immunology)
- Child
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Genotype
- HLA Antigens
(genetics, immunology)
- High-Throughput Nucleotide Sequencing
- Humans
- Immunity
(genetics)
- Influenza Vaccines
(adverse effects)
- Influenza, Human
(immunology, prevention & control)
- Male
- Middle Aged
- Narcolepsy
(etiology, metabolism, physiopathology)
- Neurons
(metabolism)
- Polymorphism, Single Nucleotide
- Young Adult
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