Investigating the shared genetic architecture between frailty and insomnia

Zhiwei Song; Wangyu Li; Yupeng Han; Yiya Xu; Yinzhou Wang

doi:10.3389/fnagi.2024.1358996

Investigating the shared genetic architecture between frailty and insomnia

Front Aging Neurosci. 2024 Feb 15:16:1358996. doi: 10.3389/fnagi.2024.1358996. eCollection 2024.

Authors

Zhiwei Song¹, Wangyu Li², Yupeng Han³, Yiya Xu¹, Yinzhou Wang^{1

4}

Affiliations

¹ Department of Neurology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
² Department of Pain Management, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
³ Department of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
⁴ Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China.

Abstract

Background: The epidemiological association between frailty and insomnia is well established, yet the presence of a common genetic etiology is still uncertain. Further exploration is needed to ascertain the causal relationship between frailty and insomnia.

Methods: Utilizing data obtained from genome-wide association studies (GWAS) summaries, we utilized the linkage disequilibrium score regression (LDSC) to determine the genetic correlation existing between frailty and insomnia. The determination of causality was achieved through the application of two-sample Mendelian randomization. We investigated the enrichment of single nucleotide polymorphism (SNP) at various tissue types utilizing stratified LD score regression (S-LDSC) and multimarker analysis of genome annotation (MAGMA). Common risk SNPs were identified using Multi-Trait Analysis of GWAS (MTAG) and Cross-Phenotype Association (CPASSOC). We further investigated the expression profiles of risk genes in tissues using Summary-data-based Mendelian randomization(SMR) based on pooled data, to explore potential functional genes.

Results: Our findings indicated a significant genetic correlation between frailty and insomnia, highlighting SNPs sharing risk (rs34290943, rs10865954), with a pronounced correlation in the localized genomic region 3p21.31. Partitioned genetic analysis revealed 24 functional elements significantly associated with both frailty and insomnia. Furthermore, mendelian randomization revealed a causal connection between frailty and insomnia. The genetic correlation between frailty and insomnia showed enrichment in 11 brain regions (S-LDSC) and 9 brain regions (MAGMA), where four functional genes (RMB6, MST1R, RF123, and FAM212A) were identified.

Conclusion: This study suggests the existence of a genetic correlation and common risk genes between frailty and insomnia, contributing to a deeper comprehension of their pathogenesis and assists in identifying potential therapeutic targets.

Keywords: Mendelian randomization; causal relationship; frailty; insomnia; shared genetic architecture.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financially supported in part by research grants from Natural Science Foundation of Fujian Province, China (2023J02024) and Medical Innovation Project of Fujian Province (2022CXA047).