Dysregulated Gene Expression: A Candidate Mechanism for Anxiety Disorders

TL;DR

This paper reviews how disrupted gene regulation, rather than single gene mutations, may contribute to anxiety disorders, offering new insights into their genetic basis.

Contribution

The paper highlights gene-regulatory elements as a novel mechanism for anxiety disorders beyond traditional single-gene variants.

Findings

Most GWAS hits for anxiety disorders are in non-coding regions linked to gene regulation.

Altered gene expression through regulatory elements may disrupt neuronal signaling and stress responses.

Understanding gene regulation could lead to better diagnosis and treatment of anxiety disorders.

Abstract

Anxiety disorders are among the most prevalent and debilitating mental illnesses worldwide. While environmental factors such as early-life stress contribute to their etiology, genetics also plays a crucial role, with a family history increasing susceptibility. Unlike Mendelian traits driven by single gene variants, anxiety disorders appear to follow polygenic inheritance in which multiple genetic variants collectively shape risk. Genome-wide association studies (GWAS) have identified numerous loci linked to anxiety, yet individual variants have small effect sizes and leave much of the heritability unexplained. A clue to resolving this conundrum may lie in the fact that most GWAS hits reside in non-coding regions with characteristics of gene-regulatory elements. This observation raises the possibility that altered expression of otherwise normal genes contributes to susceptibility. Gene-regulatory elements control when and where genes are expressed. Disruption of these elements may contribute to anxiety disorders by subtly altering neuronal signaling and stress-response pathways. Unraveling the role of gene regulation in anxiety disorders presents a promising avenue for improved diagnosis and targeted treatments. This review explores recent advances in the field and their potential for understanding the genetic architecture of anxiety disorders.

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