Sleep research article
Population-Specific Genetic and Non-Genetic Influences on Sleep Traits and Health Outcomes
Authors: Jiheum Park , Stephanie Y. Shue , Rocio Barragan , Jeong Yun Yang , Tian Gu , Chin Hur , Marie-Pierre St-Onge
One-line summary
A sleep science research article on Population-Specific Genetic and Non-Genetic Influences on Sleep Traits and Health Outcomes.
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Original abstract
Sleep traits are shaped by genetic and environmental factors and may influence many health conditions. The All of Us Research Program, which includes EHR, physical measurements, genomic data, and wearable data across ancestry groups, provides an opportunity to study genetic and non-genetic contributors to sleep-related health outcomes. We examined associations between genetic predispositions to chronotype, sleep duration, and short sleep and health outcomes across ancestries, as well as the role of measured sleep duration. We used All of Us genome-wide association study results, including ancestry-specific and meta-analyses for 3,414 phenotypes, to identify phenotypes associated with 455 sleep-related SNPs. Cross-sectional and longitudinal analyses (n = 212,529) evaluated associations between polygenic risk scores (PRS) and anthropometric and metabolic measures from EHR. A subgroup analysis (n = 7,655) assessed sleep duration using Fitbit data. Across six ancestry groups, SNP analysis identified 61 phenotypes linked to 29 sleep-trait-associated SNPs. The chronotype SNP rs1421085 in FTO showed the strongest associations with obesity, diabetes, and cardiovascular conditions, mainly in European, American, and African groups. PRS analysis showed that higher predisposition to shorter sleep duration was associated with increased risk of obesity and diabetes, with ancestry-specific variation. Measured sleep duration attenuated these associations, with relative contributions of 85.6%-99.9% in cross-sectional analyses and 7.1%-44.0% in longitudinal analyses compared with PRS. This study identified health conditions associated with genetic predispositions to sleep traits and suggests that actual sleep duration may play a prominent role in sleep-related health outcomes. Differences among meta-, pooled-, and ancestry-specific analyses highlight the importance of population-specific research.
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