BACKGROUND: There is growing evidence to support the link between anxiety and an increased risk of cognitive decline. But the genetic mechanism of this association is still unclear. Our study explores the shared genetic structure and causal relationship between anxiety and cognitive function.
METHODS: The genetic correlation between anxiety and cognitive function was assessed using linkage disequilibrium score regression (LDSC) and High-Definition Likelihood (HDL) based on data from genome-wide association studies (GWAS). The causal association was explored by bi-directional Mendelian randomization (MR). Common risk loci were identified through cross-trait meta-analyses. Stratified LDSC and multi-marker gene annotation analyses were applied to investigate single-nucleotide polymorphisms enrichment across tissue types, cell types, and functional categories. Finally, we explored shared functional genes by Summary-databased MR (SMR).
RESULTS: We found a significant negative genetic correlation between anxiety and cognitive function and that MR supports the harmful effects of anxiety on cognitive function (β = -0.121, P = 7.59 × 10). Cross-trait meta-analysis yielded 4 novel shared functional SNPs, and the functional gene ITIH4 was consistently identified in SMR. The tissue-specific heritability enrichment analysis revealed that anxiety and cognitive function were enriched in brain regions such as the frontal cortex, hypothalamus, anterior cingulate cortex and cortex, and at the cellular level, GABAergic neurons and astrocytes emerge as key cell types. -3
CONCLUSION: Our study reveals a common genetic basis between anxiety and cognitive function, including genetic correlations and common genes. These insights provide new opportunities and avenues for future study of their comorbidities.
