Investigating the shared genetic architecture between depression and subcortical volumes

Area of Science:

• Neurogenetics
• Psychiatric Disorders
• Brain Imaging

Background:

• Depression is a highly heritable mental health condition affecting millions globally.
• Neuroimaging studies indicate volumetric abnormalities in subcortical structures in depression.
• The shared genetic basis between depression and subcortical volumes is not well understood.

Purpose of the Study:

• To investigate the polygenic overlap between depression and 14 subcortical volumetric phenotypes.
• To identify shared genomic loci contributing to both depression and subcortical volumes.

Main Methods:

• Utilized the bivariate causal mixture model (MiXeR) on summary statistics from large genome-wide association studies.
• Analyzed depression (N=674,452) and 14 subcortical volumetric phenotypes (N=33,224).
• Employed conditional/conjunctional False Discovery Rate (FDR) analyses to pinpoint shared genetic loci.

Main Results:

• Subcortical volumetric traits share a substantial proportion of genetic variants with depression.
• Identified 44 distinct shared genomic loci through conjunctional FDR analysis.
• These loci are primarily in intronic and non-coding RNA intronic regions, implicating 269 protein-coding genes.

Conclusions:

• Established a shared genetic architecture between depression and subcortical volumetric phenotypes.
• Highlighted specific gene expression patterns linked to depression, subcortical volumes, and cognitive/behavioral symptoms.
• Advanced understanding of the neurobiological underpinnings of depression through genetic insights.