Faculty, Staff and Student Publications
Language
English
Publication Date
1-1-2026
Journal
Atherosclerosis
DOI
10.1016/j.atherosclerosis.2025.120603
PMID
41325697
PMCID
PMC12757440
PubMedCentral® Posted Date
1-3-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
Background and aims: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.
Methods: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20 % of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for one-degree of freedom tests of interaction and two-degree of freedom joint tests of the SNP-main and -interaction effect on lipid levels.
Results: The one-degree of freedom variant-sleep interaction test identified 10 novel loci (Pint< 5.0e-9), and we additionally identify 7 loci within the two-degree of freedom analyses (Pjoint< 5.0e-9 in combination with Pint< 6.6e-6). Multiple loci, including those mapped to APSH (target for aspartic and succinic acid) and SLC8A1 showed biological plausibility and druggability potential based on literature.
Conclusions: Collectively, the 17 (9 with short and 8 with long sleep) loci provided evidence into the biomolecular mechanisms underlying sleep-associated lipid changes, including potential involvement of the vitamin D receptor pathway. Collectively, these findings may contribute developing novel interventions for treating dyslipidemia in people with sleep disturbances.
Keywords
Humans, Genome-Wide Association Study, Male, Female, Sleep, Polymorphism, Single Nucleotide, Middle Aged, Dyslipidemias, Genetic Predisposition to Disease, Triglycerides, Lipids, Adult, Aged, Genetic Loci, Phenotype, Cholesterol, LDL, Cholesterol, HDL, Biomarkers, Sleep Wake Disorders
Published Open-Access
yes
Recommended Citation
Noordam, Raymond; Wang, Wenyi; Nagarajan, Pavithra; et al., "Genome-Wide Gene-Sleep Interaction Study Identifies Novel Lipid Loci in 732,564 Participants" (2026). Faculty, Staff and Student Publications. 1139.
https://digitalcommons.library.tmc.edu/uthsph_docs/1139