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Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy
Hyun Hor1, Zoltán Kutalik, Yves Dauvilliers
1Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
Narcolepsy, a sleep disorder, has a strong genetic link. Researchers identified a protective human leukocyte antigen (HLA) variant, suggesting the HLA region is crucial for narcolepsy susceptibility.
Area of Science:
- Genetics
- Immunology
- Neurology
Background:
- Narcolepsy is a rare sleep disorder with a strong human leukocyte antigen (HLA) association.
- The common HLA-DRB1*1501-DQB1*0602 haplotype is necessary but not sufficient for narcolepsy development.
Purpose of the Study:
- To further define the genetic basis of narcolepsy risk.
- Investigate the role of HLA variants in narcolepsy susceptibility.
Main Methods:
- Genome-wide association study (GWAS) in European narcolepsy cases and controls.
- Replication study in individuals heterozygous for HLA-DRB1*1501-DQB1*0602.
- Analysis of genetic linkage and haplotype associations.
Main Results:
- A protective variant near HLA-DQA2 (rs2858884) was identified.
- This variant is strongly linked to HLA-DRB1*03-DQB1*02 and HLA-DRB1*1301-DQB1*0603.
- Narcolepsy cases rarely carried a trans HLA-DRB1*1301-DQB1*0603 haplotype.
Conclusions:
- An unexpected protective HLA haplotype was discovered.
- The HLA region plays a virtually causal role in narcolepsy susceptibility.
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