Research Project:
Evolutionary Insights into the Genetics of Sleep Phase Disorders Using Cactus447way Genome Alignments and the UK Biobank Sleep Cohort

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Research Outline:Sleep phase disorders, such as advanced or delayed sleep phase syndrome, are complex traits influenced by both genetic and environmental factors. Despite growing interest, the genetic mechanisms underlying variation in sleep timing across individuals remain incompletely understood. Importantly, evolutionary conservation of circadian genes across species offers a promising lens through which to prioritize functionally relevant variants.This project aims to investigate the evolutionary and genetic architecture of sleep phase disorders by integrating cross-species genome alignments (Cactus447way) with large-scale human genomic data from the UK Biobank sleep cohort.Research questions:1. Are variants associated with sleep phase traits enriched in evolutionarily conserved regions?2. Do diurnal- or nocturnal-specific variants identified in the Cactus447way alignment have predictive or functional relevance in human sleep phenotypes?Objectives:- To identify variants from conserved genomic regions and those specific to diurnal or nocturnal species using the Cactus447way alignment.- To map these variants to orthologous human loci.- To test for associations between these conserved/specific variants and sleep-related phenotypes in the UK Biobank cohort.- To explore whether conservation status improves the interpretability or predictive value of sleep trait-associated loci.Scientific rationale:By integrating evolutionary conservation with human population-scale data, this study will enhance understanding of the genetic regulation of circadian rhythms and sleep disorders. Leveraging comparative genomics alongside the deep phenotyping of the UK Biobank cohort may uncover biologically meaningful variants that would be missed by conventional genome-wide association studies (GWAS) alone.

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