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Investigating the shared genetic architecture between frailty and insomnia
Zhiwei Song1, Wangyu Li2, Yupeng Han3
1Department of Neurology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
Frontiers in Aging Neuroscience
|March 1, 2024
Summary
This study reveals a shared genetic basis between frailty and insomnia, indicating a causal relationship. Identifying common risk genes offers new therapeutic targets for these interconnected conditions.
Area of Science:
- Genetics
- Gerontology
- Sleep Medicine
Background:
- Epidemiological studies confirm an association between frailty and insomnia.
- However, a common genetic etiology underlying both conditions remains unconfirmed.
- Further research is crucial to establish a causal link between frailty and insomnia.
Purpose of the Study:
- To investigate the genetic correlation and causality between frailty and insomnia.
- To identify shared genetic risk factors and functional genes implicated in both conditions.
- To explore the tissue-specific enrichment of genetic associations related to frailty and insomnia.
Main Methods:
- Genome-wide association studies (GWAS) summary data were analyzed using linkage disequilibrium score regression (LDSC).
- Two-sample Mendelian randomization was employed to assess causality.
- Stratified LD score regression (S-LDSC) and MAGMA were used for SNP enrichment analysis in various tissues.
- Multi-Trait Analysis of GWAS (MTAG) and Cross-Phenotype Association (CPASSOC) identified common risk SNPs.
- Summary-data-based Mendelian randomization (SMR) explored expression profiles of risk genes.
Main Results:
- A significant genetic correlation was found between frailty and insomnia, with shared risk SNPs identified (e.g., rs34290943, rs10865954) particularly in the 3p21.31 region.
- Partitioned genetic analysis identified 24 functional elements associated with both conditions.
- Mendelian randomization confirmed a causal relationship between frailty and insomnia.
- Genetic correlation analysis revealed enrichment in 11 (S-LDSC) and 9 (MAGMA) brain regions.
- Four functional genes (RMB6, MST1R, RF123, FAM212A) were identified as potentially involved.
Conclusions:
- This study provides evidence for a shared genetic basis between frailty and insomnia.
- The identification of common risk genes advances the understanding of their pathogenesis.
- These findings may aid in developing novel therapeutic strategies targeting shared genetic pathways.
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