Investigating the shared genetic architecture between frailty and insomnia

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

doi:10.3389/fnagi.2024.1358996

Frontiers in Aging Neuroscience (Feb 2024)

Investigating the shared genetic architecture between frailty and insomnia

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

Affiliations

Zhiwei Song: Department of Neurology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
Wangyu Li: Department of Pain Management, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
Yupeng Han: Department of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
Yiya Xu: Department of Neurology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
Yinzhou Wang: Department of Neurology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
Yinzhou Wang: Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China

DOI: https://doi.org/10.3389/fnagi.2024.1358996
Journal volume & issue: Vol. 16

Abstract

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BackgroundThe 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.MethodsUtilizing 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.ResultsOur 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.ConclusionThis 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.

Published in Frontiers in Aging Neuroscience

ISSN: 1663-4365 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.frontiersin.org/journals/aging-neuroscience

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