Shared mechanisms across the major psychiatric and neurodegenerative diseases

• Published in: Nature communications Vol. 13; no. 1; p. 4314
• Main Authors: Wingo, Thomas S., Liu, Yue, Gerasimov, Ekaterina S., Vattathil, Selina M., Wynne, Meghan E., Liu, Jiaqi, Lori, Adriana, Faundez, Victor, Bennett, David A., Seyfried, Nicholas T., Levey, Allan I., Wingo, Aliza P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.07.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 692/617/375/365/1283; 692/699/476/1414; 692/699/476/1830; 82/58; Brain; Disease; Epidemiology; Etiology; Genetic Predisposition to Disease; Genome-Wide Association Study - methods; Health risks; Health services; Humanities and Social Sciences; Humans; Mental disorders; Mental Disorders - genetics; multidisciplinary; Neurodegenerative diseases; Neurodegenerative Diseases - genetics; Pathophysiology; Polymorphism, Single Nucleotide; Protein folding; Protein interaction; Proteins; Proteomes; Proteomics; Science; Science (multidisciplinary); Transcriptomes; Transcriptomics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-31873-5

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. Studying the shared genetic etiology of disease can help improve diagnosis and treatment. Here, the authors find evidence for shared genetic and molecular pathophysiology between several common psychiatric and neurodegenerative diseases using results of 25 GWAS and large-scale human brain transcriptomic and proteomic sequencing.