Cell group analysis reveals changes in upper-layer neurons associated with schizophrenia
Posted 23 Oct 2020
bioRxiv DOI: 10.1101/2020.10.22.351213
Posted 23 Oct 2020
Genome-wide association studies (GWAS) of schizophrenia (SCZ) have revealed over 100 risk loci. We investigated whether these SCZ-associated variants regulate gene expression by cell type. Using a fully unsupervised deconvolution method, we calculated gene expression by clusters of estimated cell types (cell-groups, CGs). Five CGs emerged in the dorsolateral prefrontal cortices (DLPFC) of 341 donors with and without SCZ. By mapping expression quantitative trait loci (eQTL) per CG, we partitioned the heritability of SCZ risk in GWAS by CGs. CG-specific expressions and eQTLs were replicated in both a deconvoluted bulk tissue data set with a different method and also in sorted-cell expression data. Further, we characterized CG-specific gene differential expression and cell proportion changes in SCZ brains. We found upper-layer neurons in the DLPFC to be associated with SCZ based on enrichment of SCZ heritability in eQTLs, disease-related transcriptional signatures, and decreased cell proportion. Our study suggests that neurons and related anomalous circuits in the upper layers of the DLPFC may have a major contribution to SCZ risk.
- Downloaded 193 times
- Download rankings, all-time:
- Site-wide: 115,853
- In genomics: 6,517
- Year to date:
- Site-wide: 44,696
- Since beginning of last month:
- Site-wide: 53,943
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!