Systematic dissection of pleiotropic loci and critical regulons in excitatory neurons and microglia relevant to neuropsychiatric and ocular diseases.

ABSTRACT: Advancements in single-cell multimodal techniques have greatly enhanced our understanding of disease-relevant loci identified through genome-wide association studies (GWASs). To investigate the biological connections between the eye and brain, we integrated bulk and single-cell multiomic profiles with GWAS summary statistics for eight neuropsychiatric and five ocular diseases. Our analysis uncovered five latent factors explaining 61.7% of the genetic variance across these 13 diseases, revealing diverse correlational patterns among them. We identified 45 pleiotropic loci with 91 candidate genes that contribute to disease risk. By integrating GWAS and single-cell profiles, we implicated excitatory neurons and microglia as key contributors in the eye-brain connections. Polygenic enrichment an

SUBMITTER: Ma Y 

PROVIDER: S-EPMC11760387 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature