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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Common variants in P2RY11 are associated with narcolepsy.
Birgitte R Kornum1, Minae Kawashima, Juliette Faraco
1Center for Sleep Sciences and Department of Psychiatry, Stanford University School of Medicine, Palo Alto, California, USA.
Nature Genetics
|December 21, 2010
Summary
Narcolepsy with cataplexy may be an autoimmune disease. A genetic variant in the P2RY11 gene is linked to narcolepsy and affects immune cell survival, suggesting a role in the disease.
Area of Science:
- Genetics
- Immunology
- Neurology
Background:
- Narcolepsy with cataplexy is increasingly recognized as an autoimmune disorder.
- Genetic factors play a significant role in the susceptibility to narcolepsy.
Purpose of the Study:
- To identify genetic associations with narcolepsy with cataplexy across diverse ethnic groups.
- To investigate the functional consequences of identified genetic variants on immune cell function.
Main Methods:
- Genome-wide association studies (GWAS) were conducted in European, Asian, and African American populations.
- Replication and fine mapping were performed to confirm associations.
- Gene expression and cell survival assays were used to assess the functional impact of the associated variant.
Main Results:
- A single nucleotide polymorphism (SNP) in the 3' untranslated region of the P2RY11 gene (rs2305795) was significantly associated with narcolepsy.
- The disease-associated allele correlated with reduced P2RY11 expression in CD8(+) T lymphocytes and natural killer (NK) cells.
- This reduced expression was linked to decreased P2RY11-mediated resistance to ATP-induced cell death in these immune cells.
Conclusions:
- P2RY11 is identified as a key regulator of immune cell survival.
- The findings suggest a potential role for P2RY11 in the pathogenesis of narcolepsy with cataplexy.
- This research may have implications for understanding other autoimmune diseases.
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