A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations.

Summary

In a multi-ancestry genome-wide interaction study (n=811,405), investigators identified 22 novel loci where genetic effects on blood pressure depend on sleep duration, with non-overlapping signals for short versus long sleep. Several loci showed population- or sex-specific interactions, implicating neurological, thyroidal, bone metabolism, and hematopoietic pathways in sleep-related BP regulation.

Key Findings

• Identified 22 novel gene-by-sleep duration interaction loci for systolic, diastolic, and pulse pressure across 811,405 participants.
• Short- and long-sleep interaction loci did not overlap (12 for short sleep; 10 for long sleep), indicating distinct biological influences.
• Several loci exhibited population- or sex-specific interactions, implicating neurological, thyroidal, bone metabolism, and hematopoietic pathways for BP regulation tied to sleep.

Clinical Implications

Supports integrating sleep duration assessment into hypertension risk stratification; suggests potential for targeted interventions in genetically susceptible individuals with short or long sleep.

Limitations

• Observational genetic design cannot establish causality; sleep duration likely self-reported in contributing cohorts.
• Functional validation of implicated pathways and loci remains to be completed.

Future Directions

Functional studies of novel loci, mechanistic dissection of short vs long sleep pathways, and clinical trials testing sleep-targeted interventions in genetically at-risk groups.