Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.

Summary

Across 732,564 participants from 55 cohorts, genome-wide interaction meta-analyses identified 17 loci where genetic effects on lipids depend on short or long sleep. The results implicate vitamin D receptor–related signaling in sleep-associated lipid perturbations, suggesting new mechanistic targets for dyslipidemia among individuals with atypical sleep duration.

Key Findings

• Meta-analyses across 55 cohorts (N=732,564) identified 17 sleep-sensitive lipid loci (9 with short sleep, 8 with long sleep).
• One-degree-of-freedom interaction tests detected 10 novel loci beyond main-effect signals.
• Findings implicate vitamin D receptor–related pathways in sleep-associated lipid changes, highlighting potential therapeutic targets.

Clinical Implications

While immediate clinical practice change is premature, the identified loci and implicated pathways could guide precision prevention or therapeutics for dyslipidemia in patients with short/long sleep. It also supports integrating sleep assessment into cardiometabolic risk profiling.

Limitations

• Sleep duration was derived from cohort-specific standardized self-report, which may introduce measurement error.
• Predominantly European ancestry (87%) limits generalizability; functional validation of implicated pathways is needed.

Future Directions

Functional validation of the identified loci, cross-ancestry replication, and interventional studies targeting implicated pathways (e.g., vitamin D receptor signaling) in individuals with short/long sleep.