Association between telomere length and insomnia: A mendelian randomization and colocalization study

Previous studies have suggested a potential association between sleep and telomere length (TL), but its genetic basis remains unclear. In this study, we aimed to explore the genetic correlation and potential causal association between TL and insomnia.The genome-wide association study (GWAS) datasets of TL and insomnia-related traits were used, including insomnia, snoring, daytime dozing and napping. Based on the polygenic risk scores (PRS) of TL, linear regression and linkage disequilibrium score (LDSC) regression were used to preliminarily explore the association between TL and insomnia parameters in the UK Biobank cohort. Then, we investigated the causal association between TL and insomnia by mendelian randomization (MR) analysis and colocalization analysis.In the UK Biobank cohort, the association between TL and insomnia was observed in the female samples (t = 2.968, P = 3.00 × 10-3). LDSC detected a genetic correlation between short TL and insomnia (Rg = -9.27 × 10-2, P = 8.00 × 10-4). We found no evidence supporting significant causal association between insomnia and TL in IVW method (b = -5.95 × 10-3, P = 0.57), with horizontal pleiotropy and heterogeneity tests indicating the validity of our MR study. Finally, rs12638862 was classified as colocalized by COLOC (PP4 = 0.99), and TERC may be involved in regulating the association between insomnia and TL.Our study found no evidence for causal association between insomnia and TL in individuals of European ancestry. We detected a candidate gene associated with both insomnia and TL, providing novel clues for understanding the roles of this association.