RT Journal Article
SR Electronic
T1 Genetics of vaccination-related narcolepsy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 169623
DO 10.1101/169623
A1 Hanna M. Ollila
A1 Annika Wennerstrom
A1 Markku Partinen
A1 Emmanuel Mignot
A1 Janna Saarela
A1 Turkka Kirjavainen
A1 Christer Hublin
A1 Logan D. Schneider
A1 Sari-Leena Himanen
A1 Outi Saarenpää-heikkilä
A1 Paivi Saavalainen
A1 Pentti J. Tienari
A1 Outi Vaarala
A1 Markus Perola
YR 2017
UL http://biorxiv.org/content/early/2017/07/28/169623.abstract
AB Narcolepsy type 1 is a severe hypersomnia affecting 1/3000 individuals. It is caused by a loss of neurons producing hypocretin/orexin in the hypothalamus. In 2009/2010, an immunization campaign directed towards the new pandemic H1N1 Influenza-A strain was launched and increased risk of narcolepsy reported in Northern European countries following vaccination with Pandemrix®, an adjuvanted H1N1 vaccine resulting in ~250 vaccination-related cases in Finland alone. Using whole genome sequencing data of 2000 controls, exome sequencing data of 5000 controls and HumanCoreExome chip genotypes of 81 cases with vaccination-related narcolepsy and 2796 controls, we, built a multilocus genetic risk score with established narcolepsy risk variants. We also analyzed, whether novel risk variants would explain vaccine-related narcolepsy. We found that previously discovered risk variants had strong predictive power (accuracy of 73% and P<2.2*10−16; and ROC curve AUC 0.88) in vaccine-related narcolepsy cases with only 4.9% of cases being assigned to the low risk category. Our findings indicate genetic predisposition to vaccine-triggered narcolepsy, with the possibility of identifying 95% of people at risk.