Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure

Area of Science:

• Genetics
• Cardiovascular Science
• Sleep Medicine

Background:

• Sleep duration is linked to elevated blood pressure (BP), potentially via neuroendocrine and vascular pathways.
• Understanding the genetic basis of sleep-related BP variation is crucial for identifying novel regulatory mechanisms.

Purpose of the Study:

• To identify novel genes interacting with short or long sleep duration to influence blood pressure traits.
• To explore the genetic architecture of sleep-related BP variation across diverse ancestry groups.

Main Methods:

• Genome-wide gene-by-sleep duration interaction analyses were conducted on four BP traits.
• Two-stage design involving a 2 degrees of freedom (df) joint test followed by a 1df test of interaction effects.
• Analyses were performed across five ancestry groups, totaling 122,265 individuals.

Main Results:

• Three novel gene-sleep interactions were identified and replicated, including associations with FIGNL2/ANKRD33, SNORA26/C9orf170, and KCTD15/LSM14A.
• An additional novel gene-sleep interaction (TRPC3/KIAA1109) was found in individuals of African ancestry.
• Multiple loci previously associated with BP showed significant gene-sleep interactions, highlighting shared genetic pathways.

Conclusions:

• Sleep duration and genetic factors interact to regulate blood pressure, influencing cardiovascular health.
• This research provides novel insights into the molecular mechanisms underlying sleep-related BP regulation.
• Findings suggest potential therapeutic targets for managing hypertension by considering sleep patterns.