Disease Modules Associated with Unfavorable Sleep Patterns and Their Genetic Determinants: A Prospective Cohort Study of the UK Biobank.

Abstract

Despite the established associations between sleep-related traits and major diseases, comprehensive assessment on affected disease modules and their genetic determinants is lacking. Using multiple correspondence analysis and the k-means clustering algorithm, 235,826 eligible participants were clustered into distinct unfavorable sleep patterns [short sleep duration (n = 10,073), snoring (22,419), insomnia (102,771), insomnia and snoring (62,909)] and favorable sleep pattern groups (37,654). The associations of unfavorable sleep patterns with 134 diseases were estimated using Cox regression models; and comorbidity network analyses were applied for disease module identification. Genetic determinants associated with each disease module were identified by genome-wide association studies (GWAS). During an average follow-up of 10.80 years, unfavorable sleep patterns featured by 'short sleep duration', 'snoring', 'insomnia', and 'insomnia and snoring' were associated with increased risk of 0, 9, 10, and 19 diseases, respectively. Furthermore, comorbidity network analyses categorized these affected diseases into three disease modules, characterized by predominant diseases related to digestive system, circulatory and endocrine systems (snoring-related patterns only), and musculoskeletal system (insomnia-related patterns only). Using the number of affected diseases, as an index of a person's susceptibility to each disease module [i.e., susceptible score (SS)], GWAS analyses identified five, one, and three significant loci associated with the residual SS of these aforementioned disease modules, respectively, which mapped to several potential biological pathways, including those related to hormone regulation and catecholamine uptake. In conclusion, individuals with unfavorable sleep patterns, particularly snoring and insomnia, had increased risk of multiple diseases. The identification of three major disease modules with their relevant genetic determinants may facilitate strategy development for precision prevention of future health decline.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-023-00144-8.