Population-Specific Genetic and Non-Genetic Influences on Sleep Traits and Health Outcomes

Area of Science:

• Genetics and Sleep Science
• Population Health Research

Background:

• Sleep traits are influenced by genetic and environmental factors, impacting various health conditions.
• The All of Us Research Program offers a unique dataset including EHR, genomic, and wearable data across diverse ancestry groups.

Purpose of the Study:

• To investigate the associations between genetic predispositions for sleep traits (chronotype, sleep duration, short sleep) and health outcomes across different ancestries.
• To evaluate the role of measured sleep duration in mediating these genetic associations.

Main Methods:

• Utilized All of Us genome-wide association study results to identify phenotypes associated with sleep-related single nucleotide polymorphisms (SNPs).
• Conducted cross-sectional and longitudinal analyses using polygenic risk scores (PRS) and electronic health records (EHR) data (n=212,529).
• Performed subgroup analysis on measured sleep duration using Fitbit data (n=7,655).

Main Results:

• Identified 61 phenotypes linked to 29 sleep-trait-associated SNPs across six ancestry groups.
• The FTO SNP rs1421085 (chronotype) showed strong associations with obesity, diabetes, and cardiovascular conditions, particularly in European, American, and African groups.
• Higher genetic predisposition to shorter sleep duration correlated with increased obesity and diabetes risk, with variations across ancestries. Measured sleep duration substantially attenuated these PRS associations.

Conclusions:

• Genetic predispositions to sleep traits are associated with specific health conditions.
• Measured sleep duration plays a significant role in mediating the relationship between genetic sleep predispositions and health outcomes.
• Population-specific analyses are crucial for understanding the complex interplay of genetics, sleep, and health across diverse groups.