Beyond Chronotype: Complex Genetic Influences on Sleep Architecture in Healthy Adults

Objectives: This study aimed to examine the relationship between comprehensive genetic risk profiles and sleep parameters in healthy young adults.Methods: This study included 85 healthy Korean adults (mean age 28.18±4.3 years, 77.6% female). The participants completed validated self-report questionnaires and 14-day sleep diaries. Genetic testing was performed using direct-to-consumer panels to analyze 230 health-related and 317 disease-related markers. Three complementary analytical approaches were employed: Spearman’s correlations between ordinal genetic risk scores and sleep parameters, group-based analysis of variance (ANOVA) to compare sleep variables across genetic risk groups, and individual single-nucleotide polymorphism–level analyses. Associations were required to demonstrate consistent directional trends across ≥3 sleep parameters for inclusion.Results: Significant and consistent correlations with three or more sleep parameters were observed for the following genetic markers: calcium deficiency, coenzyme Q10 (CoQ10) deficiency, nicotine metabolism, chronotype, gallbladder cancer, and skin cancer. Comprehensive analysis revealed three distinct genetic-sleep phenotypes: 1) compensatory patterns in which metabolic deficiencies (calcium and CoQ10) were associated with altered sleep architecture; 2) pharmacological validation of nicotine metabolism; and 3) disease susceptibility paradoxes, where variants associated with health risks demonstrated superior sleep outcomes.Conclusions: These findings represent a paradigm shift emphasizing that genetic architecture involves complex trade-offs between different physiological systems, with profound implications for personalized sleep medicine that moves beyond one-size-fits-all approaches toward treatment strategies optimized for individual genetic profiles.