{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:17:32Z","timestamp":1790299052894,"version":"4.1.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901294"],"award-info":[{"award-number":["81901294"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Epidemiological and clinical studies have suggested comorbidity between schizophrenia and several neurodegenerative disorders. However, little is known whether there exists shared genetic architecture. To explore their relationship from a genetic and transcriptomic perspective, we applied polygenic and linkage disequilibrium-informed methods to examine the genetic correlation between schizophrenia and amyotrophic lateral sclerosis (ALS), Parkinson\u2019s disease, Alzheimer\u2019s disease and frontotemporal dementia. We further combined genome-wide association summary statistics with large-scale transcriptomic datasets, to identify putative shared genes and explore related pathological tissues. We identified positive and significant correlation between schizophrenia and ALS at genetic (correlation 0.22; 95% CI: 0.16\u20130.28; <jats:italic>p<\/jats:italic> = 4.00E-04) and transcriptomic (correlation 0.08; 95% CI: 0.04\u20130.11; <jats:italic>p<\/jats:italic> = 0.034) levels. We further demonstrated that schizophrenia- and ALS-inferred gene expression overlap significantly in four tissues including skin, small intestine, brain cortex and lung, and highlighted three genes, namely <jats:italic>GLB1L3<\/jats:italic>, <jats:italic>ZNHIT3<\/jats:italic> and <jats:italic>TMEM194A<\/jats:italic> as potential mediators of the correlation between schizophrenia and ALS. Our findings revealed overlapped gene expression profiles in specific tissues between schizophrenia and ALS, and identified novel potential shared genes. These results provided a better understanding for the pleiotropy of schizophrenia, and paved way for future studies to further elucidate the molecular drivers of schizophrenia.<\/jats:p>","DOI":"10.3389\/fcell.2021.797072","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T09:19:05Z","timestamp":1640337545000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Overlapping Genetic Architecture Between Schizophrenia and Neurodegenerative Disorders"],"prefix":"10.3389","volume":"9","author":[{"given":"Chunyu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianmi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruwei","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature11632","article-title":"An Integrated Map of Genetic Variation from 1,092 Human Genomes","volume":"491","author":"Abecasis","year":"2012","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1093\/brain\/awx040","article-title":"ZNHIT3 Is Defective in PEHO Syndrome, a Severe Encephalopathy with Cerebellar Granule Neuron Loss","volume":"140","author":"Anttonen","year":"2017","journal-title":"Brain"},{"key":"B3","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.nbd.2014.12.002","article-title":"Molecular Classification of Amyotrophic Lateral Sclerosis by Unsupervised Clustering of Gene Expression in Motor Cortex","volume":"74","author":"Aronica","year":"2015","journal-title":"Neurobiol. 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