Narcolepsy as a potential risk factor for Schizophrenia

Narcolepsy is a severe sleep disorder with characteristics of fatigue, fragmented sleep, cataplexy and hypnagogic hallucinations. Earlier clinical studies have reported the onset of schizophrenia after narcolepsy but the causality behind narcolepsy and schizophrenia is unknown. Our goal was to understand the causality between narcolepsy and schizophrenia. To estimate the comorbidity between narcolepsy and schizophrenia, we employed data from the FinRegistry that contains data for the total population of Finland in total 7.2 million individuals (N = 1664 individuals with narcolepsy and 55,372 with schizophrenia). We then used Mendelian randomization and previously published genome-wide association data to test the causality between narcolepsy and schizophrenia. We observed a robust causal association from narcolepsy to schizophrenia using the HLA-independent lead variants (P-value = 6.0 × 10^-4), which was accentuated when including the HLA locus (P-value = 4.48 × 10^-7). Furthermore, we observed a modest bidirectional causality from schizophrenia to narcolepsy (P-value = 0.015). There was no evidence of pleiotropy. Our findings indicate a causal relationship where narcolepsy may increase the risk for schizophrenia, and a bidirectional causality from schizophrenia to narcolepsy. Additionally, our results clarify the psychiatric burden in narcolepsy.