Investigating the shared genetic architecture between frailty and insomnia

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. Utilizing data obtained from genome-wide association st...

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Bibliographic Details
Published in:Frontiers in aging neuroscience 2024-02, Vol.16, p.1358996-1358996
Main Authors: Song, Zhiwei, Li, Wangyu, Han, Yupeng, Xu, Yiya, Wang, Yinzhou
Format: Article
Language:English
Subjects:
Aging Neuroscience
Biobanks
causal relationship
Epidemiology
Frailty
Gene loci
Genetic analysis
Genome-wide association studies
Genomes
Genotype & phenotype
Insomnia
Linkage disequilibrium
Mendelian randomization
Meta-analysis
Phenotypes
shared genetic architecture
Single-nucleotide polymorphism
Sleep
Sleep disorders
Therapeutic targets
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Summary: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. 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. 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. 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.
ISSN:1663-4365
1663-4365
DOI:10.3389/fnagi.2024.1358996