Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic.
PLoS Genet
; 9(10): e1003880, 2013 Oct.
Article
en En
| MEDLINE
| ID: mdl-24204295
ABSTRACT
Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7 × 10(-9) OR 0.77), ZNF365 (rs10995245 max P = 1.2 × 10(-11) OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2 × 10(-9) OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10(-9) beta -1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8 × 10(-10) OR 0.57). These reflected an association of DQB1*0301 with earlier onset and decreased DQB1*0602 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Gripe Humana
/
Subtipo H1N1 del Virus de la Influenza A
/
Estudio de Asociación del Genoma Completo
/
Narcolepsia
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
País/Región como asunto:
Asia
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
China