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. Issue 1 (1st January 2015) - Ollila, Hanna M.
Abstract: 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.