Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy.
Data(s) |
2010
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Resumo |
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. |
Identificador |
http://serval.unil.ch/?id=serval:BIB_CFB40FFC4F99 isbn:1546-1718[electronic], 1061-4036[linking] pmid:20711174 doi:10.1038/ng.647 isiid:000281388400016 |
Idioma(s) |
en |
Fonte |
Nature Genetics, vol. 42, no. 9, pp. 786-789 |
Palavras-Chave | #Adult; Aged; Case-Control Studies; European Continental Ancestry Group/genetics; Female; Gene Frequency; Genetic Predisposition to Disease; Genome-Wide Association Study; HLA-D Antigens/genetics; Haplotypes; Humans; Male; Middle Aged; Narcolepsy/genetics ; Colaus Study |
Tipo |
info:eu-repo/semantics/article article |