HLA-DQ Allele Competition in Narcolepsy: A Comment on Tafti et al. DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe

Study Objectives: Although HLA-DQB1* 06: 02 is the strongest predisposing genetic factor for narcolepsy, the effect of this gene must be considered alongside that of its polymorphic partner, DQA1. In this paper, we extend an analysis of the effect of HLA-DQB1 on narcolepsy risk published recently by Tafti et al. Results: Imputing allelic variation at the level of HLA-DQA1, we show that this locus also has a considerable effect on disease susceptibility. Our data are also compatible with previous findings in multi-ethnic group data sets showing that allele competition effects within the DQ1 group determine the amount of DQ0602 (the DQA1* 01: 02/DQB1* 06: 02 heterodimer), and consequently, the risk of developing narcolepsy. We also found an independent predisposing effect of DQB1* 03: 01 via a currently unknown mechanism. Conclusions: Both DQA1 and DQB1 influence narcolepsy risk.