0047 Enrichment of the LSAMP Variants in DSWPD Patients: Large Whole Genome Sequencing Analysis from a Clinical Study

Abstract Introduction We are conducting a clinical study in Delayed Sleep-Wake phase disorder (DSWPD) patients. The objective of this work was to measure sleep-wake patterns and to conduct exploratory genetic analyses to delineate the genetic landscape of the DSWPD phenotype. Methods We measured the sleep-wake patterns (self-reported bedtime, wake time, midpoint of sleep, and sleep latency) of participants by daily post-sleep diaries for 4 week screening period. Participants completed questionnaires pertaining to demographics, medical and surgical history, sleep history, and concomitant medications. Altogether, 170 participants were consented and provided samples for whole genome sequencing. Results We observed a significant enrichment of LSAMP We observed significantly higher frequencies in cases as compared to controls. Controls were defined as participants screened for not having sleep issues/nor diagnosed sleep disorders. MAF in the DSWPD cases was 0.20 versus 0.11 MAF in matched super controls. Allelic frequency varied across ancestries We have analyzed adjusting for population stratification. LSAMP variants are of particular interest as it is implicated in mood, anxiety, and tumor suppression, acting on limbic system functions like emotion and behavior, potentially by affecting cell proliferation pathways, with research suggesting its role in disorders like depression and epilepsy and seen across numerous neuropsychiatric disorders. Conclusion These results demonstrate that, on average, DSWPD individuals are more likely to harbor variants within LSAMP, potentially leading to risk for development of a pronounced delay in sleep period. This variant can further impact the response to treatments Support (if any)