An approach based on a genome-wide association study reveals candidate loci for narcolepsy
Copyright policy )An approach based on a genome-wide association study reveals candidate loci for narcolepsy
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and a pathological manifestation of rapid eye movement during sleep. Narcoleptic pathogenesis is triggered by both genetic and environmental factors. Recently, development of genome-wide association studies (GWAS) has identified new genetic factors, with many more susceptibility genes yet to be elucidated. Using a new approach that consists of a combination of GWAS and an extensive database search for candidate genes, we picked up 202 candidate genes and performed a replication study in 222 narcoleptic patients and 380 controls. Statistical analysis indicated that six genes, NFATC2, SCP2, CACNA1C, TCRA, POLE, and FAM3D, were associated with narcolepsy (P<0.001). Some of these associations were further supported by gene expression analyses and an association study in essential hypersomnia (EHS), CNS hypersonia similar to narcolepsy. This novel approach will be applicable to other GWAS in the search of disease-related susceptibility genes.
- University of Tokyo Japan
- Neuropsychiatric Research Institute United States
- Tokyo Metropolitan Institute of Medical Science Japan
- Tokyo Institute of Psychiatry Japan
- Stanford University United States
Chi-Square Distribution, Membrane Glycoproteins, Calcium Channels, L-Type, Genotype, NFATC Transcription Factors, Gene Expression Profiling, DNA Polymerase II, HLA-DR Antigens, Linkage Disequilibrium, Gene Frequency, HLA-DQ Antigens, Cytokines, HLA-DQ beta-Chains, Humans, Genetic Predisposition to Disease, Carrier Proteins, Poly-ADP-Ribose Binding Proteins, Genome-Wide Association Study, HLA-DRB1 Chains, Narcolepsy
Chi-Square Distribution, Membrane Glycoproteins, Calcium Channels, L-Type, Genotype, NFATC Transcription Factors, Gene Expression Profiling, DNA Polymerase II, HLA-DR Antigens, Linkage Disequilibrium, Gene Frequency, HLA-DQ Antigens, Cytokines, HLA-DQ beta-Chains, Humans, Genetic Predisposition to Disease, Carrier Proteins, Poly-ADP-Ribose Binding Proteins, Genome-Wide Association Study, HLA-DRB1 Chains, Narcolepsy
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