Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy
| Autor: | Peter Vollenweider, Joan Santamaria, Antonio Benetó, Stine Knudsen, Vincent Mooser, Michel Lecendreux, Hyun Hor, Sven Bergmann, Corinne Pfister, Isabelle Arnulf, Yves Dauvilliers, Peter Geisler, Claire E H M Donjacour, Gert J. Lammers, Johannes Mathis, Sebastiaan Overeem, Jacques S. Beckmann, Julie Vienne Bürki, Alex Iranzo, Mehdi Tafti, Claudio L. Bassetti, Frans H.J. Claas, Armand Valsesia, Geert Mayer, Dawn M. Waterworth, Brice Petit, Rosa Peraita Adrados, Gérard Waeber, Zoltán Kutalik, Raphael Heinzer, Gérard Didelot, Ioannis Theodorou, Michel Billiard, Guadalupe Ercilla, Poul Jennum, Willem Verduijn, José L. Vicario |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male musculoskeletal diseases Population Genome-wide association study Human leukocyte antigen Biology White People 03 medical and health sciences 0302 clinical medicine Gene Frequency immune system diseases Genetics medicine Humans Genetic Predisposition to Disease copy number variation sleep-disorders cataplexy genetics diseases risk 2nd education skin and connective tissue diseases Allele frequency Aged Narcolepsy 030304 developmental biology HLA-D Antigens 0303 health sciences education.field_of_study Haplotype Case-control study Odds ratio Middle Aged medicine.disease 3. Good health Haplotypes Case-Control Studies Immunology Female Functional Neurogenomics [DCN 2] 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Nature Genetics, 42, 9, pp. 786-9 Nature Genetics, 42, 786-9 Nature genetics Nature Genetics, 42(9), 786 |
| ISSN: | 1061-4036 |
| Popis: | Contains fulltext : 88508.pdf (Publisher’s version ) (Closed access) Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing narcolepsy. To further define the genetic basis of narcolepsy risk, we performed a genome-wide association study (GWAS) in 562 European individuals with narcolepsy (cases) and 702 ethnically matched controls, with independent replication in 370 cases and 495 controls, all heterozygous for DRB1*1501-DQB1*0602. We found association with a protective variant near HLA-DQA2 (rs2858884; P < 3 x 10(-8)). Further analysis revealed that rs2858884 is strongly linked to DRB1*03-DQB1*02 (P < 4 x 10(-43)) and DRB1*1301-DQB1*0603 (P < 3 x 10(-7)). Cases almost never carried a trans DRB1*1301-DQB1*0603 haplotype (odds ratio = 0.02; P < 6 x 10(-14)). This unexpected protective HLA haplotype suggests a virtually causal involvement of the HLA region in narcolepsy susceptibility. 01 september 2010 |
| Databáze: | OpenAIRE |
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