PLoS Genetics (Oct 2013)

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.

  • Fang Han,
  • Juliette Faraco,
  • Xiao Song Dong,
  • Hanna M Ollila,
  • Ling Lin,
  • Jing Li,
  • Pei An,
  • Shan Wang,
  • Ke Wei Jiang,
  • Zhan Cheng Gao,
  • Long Zhao,
  • Han Yan,
  • Ya Nan Liu,
  • Qing Hua Li,
  • Xiao Zhe Zhang,
  • Yan Hu,
  • Jing Yu Wang,
  • Yun Hui Lu,
  • Chang Jun Lu,
  • Wei Zhou,
  • Joachim Hallmayer,
  • Yu Shu Huang,
  • Kingman P Strohl,
  • Thomas Pollmächer,
  • Emmanuel Mignot

DOI
https://doi.org/10.1371/journal.pgen.1003880
Journal volume & issue
Vol. 9, no. 10
p. e1003880

Abstract

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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*03:01 with earlier onset and decreased DQB1*06:02 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.