Shared mechanisms across the major psychiatric and neurodegenerative diseases

• Type of Material: Article
• Authors: Thomas Wingo, Emory University; Yue Liu, Emory University; Ekaterina S Gerasimov, Emory University; Selina M Vattathil, Emory University; Meghan E Wynne, Emory University; Jiaqi Liu, Emory University; Adriana Lori, Emory University; Victor Faundez, Emory University; David A Bennett, Rush University; Nicholas Seyfried, Emory University; Allan Levey, Emory University; Aliza Wingo, Emory University
• Language: English
• Date: 2022-07-26
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-022-31873-5
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 13
• Issue: 1
• Start Page: 4314
• End Page: 4314
• Keywords: RISK LOCI; GENOME-WIDE ASSOCIATION; Science & Technology; Multidisciplinary Sciences; MITOCHONDRIA; Science & Technology - Other Topics; DEMENTIA; PARKINSONS-DISEASE; SCHIZOPHRENIA; ALZHEIMERS-DISEASE; BRAIN; BETA; POSTTRAUMATIC-STRESS-DISORDER
• Research Categories: Biology, Cell

Abstract

Several common psychiatric and neurodegenerative diseases share epidemiologic risk; however, whether they share pathophysiology is unclear and is the focus of our investigation. Using 25 GWAS results and LD score regression, we find eight significant genetic correlations between psychiatric and neurodegenerative diseases. We integrate the GWAS results with human brain transcriptomes (n = 888) and proteomes (n = 722) to identify cis- and trans- transcripts and proteins that are consistent with a pleiotropic or causal role in each disease, referred to as causal proteins for brevity. Within each disease group, we find many distinct and shared causal proteins. Remarkably, 30% (13 of 42) of the neurodegenerative disease causal proteins are shared with psychiatric disorders. Furthermore, we find 2.6-fold more protein-protein interactions among the psychiatric and neurodegenerative causal proteins than expected by chance. Together, our findings suggest these psychiatric and neurodegenerative diseases have shared genetic and molecular pathophysiology, which has important ramifications for early treatment and therapeutic development.