Journal des troubles du sommeil et de la thérapie
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Narcolepsy Associated Genetic Variants Associated with Impaired Cognition in A Community Dwelling Older Cohort

Steven Jervis*, Antony Payton, Marcus Lowe, Altug Didikoglu, Arpana Verma, Kay Poulton

Objective: Studies have hypothesised that the combination of pre-existing genetic traits and specific environmental triggers determine the onset of the Narcolepsy. The most impactful genetic risk factor is the presence of Human Leukocyte Antigen (HLA) DQB1*06:02 encoded on the Major Histocompatibility Complex (MHC), however, the presence of HLA-DQB1*06:02 is not ubiquitous in all narcolepsy cases. The most poignant genetic risk factors outside the MHC are predominantly located in genes associated with the immune system. In addition to the traditional symptoms of narcolepsy, the co-morbidities can vary with a cohort of sufferers complaining of cognitive dysfunction, particularly memory and attention. These self-report are not substantiated by consistent scientific evidence whereas there is significant evidence outlining the genetic contribution underpinning variation in cognitive abilities in the general population .

Materials and method: In this study we impute targeted non-MHC narcolepsy associated Single Nucleotide Polymorphisms (SNPs) from 1,558 non-pathological elderly volunteers who have been followed for change in cognitive function for up to a 24-year period. Specifically, we investigate 13 previously documented narcolepsy associated SNPs with an odds ratio greater than or equal to 1.00 combined with a minor allele frequency of greater than 0.05.

Results: We observed an association between rs306336, rs4290173 and rs2834168 and a faster decline in long term memory. Similarly, we observed a protective effect of rs10995245 against the decline of long-term memory loss.

Conclusion: This investigation suggests that the cognitive problems reported by cohorts of narcoleptic patients may be due to genetic predispositions and supports the variation seen in the co-morbidities associated with narcolepsy.