0035 Melanopsin genetic variants and delayed sleep phenotype – whole genome sequencing analysis

Abstract Introduction Melanopsin (OPN4) is a blue light-sensitive opsin-type G-protein coupled receptor. It highly expressed in photosensitive retinal ganglion cells which mediate responses to light, including regulation of sleep, circadian photoentrainment, and pupillary light response. Mutations OPN4 were shown affect ultimately affecting the rhythms sleep. Previously, we describe male carrier missense variant diagnosed with delayed sleep-wake phase disorder (DSWPD), consistent recurrent pattern sleep onset The rs143641898 [NM_033282.4:c.502C>T p.(Arg168Cys)] gene that was functional study render protein non-functional. Methods analysis conducted on whole genome sequencing samples obtained from patients clinical diagnosis DSWPD. Age sex-matched used as controls. Results Here report an enrichment rare coding variants, MAF< 1, set 117 DSWPD compared 315 healthy This significant likely implies other pLOFs can similarly contribute phenotype. Moreover, association rs rs1079610, common – bedtime patients. has been previously reported altered responses. effect not seen large controls without diagnosis. Conclusion discussed variants increase risk via its direct pathophysiology along melanopsin axis. offers useful insights for differential treatment carry pathogenic gene. Support (if any)