Unraveling the Shared Genetic Architecture and Polygenic Overlap Between Loneliness, Major Depressive Disorder, and Sleep-Related Traits.

ABSTRACT: Background: Loneliness (LON) is a heritable psychosocial trait that frequently co-occurs with major depressive disorder (MDD) and sleep traits. Despite known genetic contributions, the shared genetic architecture and molecular mechanisms underlying their co-occurrence remain largely unknown. This study aimed to uncover novel genetic risk loci and cross-trait gene expression effects. Methods: Large-scale genome-wide association study (GWAS) datasets were analyzed using the causal mixture model (MiXeR) to estimate polygenicity and shared genetic architecture. Genetic correlation analyses were performed using linkage disequilibrium score regression (LDSC) and local analysis of [co]variant annotation (LAVA). Conditional and conjunctional FDR methods further identified single nucl

SUBMITTER: Rehman Z 

PROVIDER: S-EPMC12730563 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature