Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. / Hor, Hyun; Kutalik, Zoltán; Dauvilliers, Yves; Valsesia, Armand; Lammers, Gert J; Donjacour, Claire E H M; Iranzo, Alex; Santamaria, Joan; Peraita Adrados, Rosa; Vicario, José L; Overeem, Sebastiaan; Arnulf, Isabelle; Theodorou, Ioannis; Jennum, Poul; Knudsen, Stine; Bassetti, Claudio; Mathis, Johannes; Lecendreux, Michel; Mayer, Geert; Geisler, Peter; Benetó, Antonio; Petit, Brice; Pfister, Corinne; Bürki, Julie Vienne; Didelot, Gérard; Billiard, Michel; Ercilla, Guadalupe; Verduijn, Willem; Claas, Frans H J; Vollenweider, Peter; Vollenwider, Peter; Waeber, Gerard; Waterworth, Dawn M; Mooser, Vincent; Heinzer, Raphaël; Beckmann, Jacques S; Bergmann, Sven; Tafti, Mehdi.
I: Nature Genetics, Bind 42, Nr. 9, 01.09.2010, s. 786-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy
AU - Hor, Hyun
AU - Kutalik, Zoltán
AU - Dauvilliers, Yves
AU - Valsesia, Armand
AU - Lammers, Gert J
AU - Donjacour, Claire E H M
AU - Iranzo, Alex
AU - Santamaria, Joan
AU - Peraita Adrados, Rosa
AU - Vicario, José L
AU - Overeem, Sebastiaan
AU - Arnulf, Isabelle
AU - Theodorou, Ioannis
AU - Jennum, Poul
AU - Knudsen, Stine
AU - Bassetti, Claudio
AU - Mathis, Johannes
AU - Lecendreux, Michel
AU - Mayer, Geert
AU - Geisler, Peter
AU - Benetó, Antonio
AU - Petit, Brice
AU - Pfister, Corinne
AU - Bürki, Julie Vienne
AU - Didelot, Gérard
AU - Billiard, Michel
AU - Ercilla, Guadalupe
AU - Verduijn, Willem
AU - Claas, Frans H J
AU - Vollenweider, Peter
AU - Vollenwider, Peter
AU - Waeber, Gerard
AU - Waterworth, Dawn M
AU - Mooser, Vincent
AU - Heinzer, Raphaël
AU - Beckmann, Jacques S
AU - Bergmann, Sven
AU - Tafti, Mehdi
PY - 2010/9/1
Y1 - 2010/9/1
N2 - 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.
AB - 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.
U2 - http://dx.doi.org/10.1038/ng.647
DO - http://dx.doi.org/10.1038/ng.647
M3 - Journal article
VL - 42
SP - 786
EP - 789
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 9
ER -
ID: 34190289