Dataset Information

Identification of Novel Genomic Loci for Anxiety and Extensive Genetic Overlap with Psychiatric Disorders.

ABSTRACT:

Background

Anxiety disorders are prevalent and anxiety symptoms often co-occur with psychiatric disorders. Here, we aimed to identify genomic risk loci associated with anxiety, characterize its genetic architecture, and genetic overlap with psychiatric disorders.

Methods

We used the largest available GWAS of anxiety (GAD-2 score), schizophrenia, bipolar disorder, major depression, and attention deficit hyperactivity disorder (ADHD). We employed MiXeR and LAVA to characterize the genetic architecture and genetic overlap between the phenotypes. Additionally, conditional and conjunctional false discovery rate analyses were performed to boost the identification of genomic loci associated with anxiety and those shared with psychiatric disorders. Gene annotation and gene set analyses were carried out using OpenTargets and FUMA, respectively.

Results

Anxiety was polygenic with 8.4k estimated genetic risk variants and overlapped extensively with psychiatric disorders (4.1-7.8k variants). Both MiXeR and LAVA revealed predominantly positive genetic correlations between anxiety and psychiatric disorders. We identified 154 anxiety loci (139 novel) by conditioning on the psychiatric disorders. We identified loci shared between anxiety and major depression (n = 66), bipolar disorder (n = 19), schizophrenia (n = 51), and ADHD (n = 37). Genes annotated to anxiety loci exhibit enrichment for a broader range of biological pathways and differential tissue expression in more diverse tissues than those annotated to the shared loci.

Conclusions

Anxiety is a highly polygenic phenotype with extensive genetic overlap with psychiatric disorders. These genetic overlaps enabled the identification of novel loci for anxiety and shared loci with psychiatric disorders. The shared genetic architecture may underlie the comorbidity of anxiety, and the identified genetic loci implicate molecular pathways that could become potential drug targets.

SUBMITTER: Tesfaye M

PROVIDER: S-EPMC10491354 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Identification of Novel Genomic Loci for Anxiety and Extensive Genetic Overlap with Psychiatric Disorders.

Tesfaye Markos M Jaholkowski Piotr P Shadrin Alexey A AA van der Meer Dennis D Hindley Guy F L GFL Holen Børge B Parker Nadine N Parekh Pravesh P Birkenæs Viktoria V Rahman Zillur Z Bahrami Shahram S Kutrolli Gleda G Frei Oleksandr O Djurovic Srdjan S Dale Anders M AM Smeland Olav B OB O'Connell Kevin S KS Andreassen Ole A OA

medRxiv : the preprint server for health sciences 20240408

<h4>Background</h4>Anxiety disorders are prevalent and anxiety symptoms co-occur with many psychiatric disorders. We aimed to identify genomic risk loci associated with anxiety, characterize its genetic architecture, and genetic overlap with psychiatric disorders.<h4>Methods</h4>We used the GWAS of anxiety symptoms, schizophrenia, bipolar disorder, major depression, and attention deficit hyperactivity disorder (ADHD). We employed MiXeR and LAVA to characterize the genetic architecture and geneti ...[more]

PMID: 37693403

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Dataset Information

Identification of Novel Genomic Loci for Anxiety and Extensive Genetic Overlap with Psychiatric Disorders.

Background

Methods

Results

Conclusions

Publications

Identification of Novel Genomic Loci for Anxiety and Extensive Genetic Overlap with Psychiatric Disorders.

Similar Datasets

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