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Citation
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HERO ID
7355910
Reference Type
Journal Article
Title
Profiling gene expression in the human dentate gyrus granule cell layer reveals insights into schizophrenia and its genetic risk
Author(s)
Jaffe, AE; Hoeppner, DJ; Saito, T; Blanpain, L; Ukaigwe, J; Burke, EE; Collado-Torres, L; Tao, R; Tajinda, K; Maynard, KR; Tran, MN; Martinowich, K; Deep-Soboslay, A; Shin, JH; Kleinman, JE; Weinberger, DR; Matsumoto, M; Hyde, TM
Year
2020
Is Peer Reviewed?
1
Journal
Nature Neuroscience
ISSN:
1097-6256
EISSN:
1546-1726
Volume
23
Issue
4
Page Numbers
510-519
Language
English
PMID
32203495
DOI
10.1038/s41593-020-0604-z
Web of Science Id
WOS:000519843200001
URL
http://www.nature.com/articles/s41593-020-0604-z
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Abstract
Specific cell populations may have unique contributions to schizophrenia but may be missed in studies of homogenate tissue. Here laser capture microdissection followed by RNA sequencing (LCM-seq) was used to transcriptomically profile the granule cell layer of the dentate gyrus (DG-GCL) in human hippocampus and contrast these data to those obtained from bulk hippocampal homogenate. We identified widespread cell-type-enriched aging and genetic effects in the DG-GCL that were either absent or directionally discordant in bulk hippocampus data. Of the ~9 million expression quantitative trait loci identified in the DG-GCL, 15% were not detected in bulk hippocampus, including 15 schizophrenia risk variants. We created transcriptome-wide association study genetic weights from the DG-GCL, which identified many schizophrenia-associated genetic signals not found in transcriptome-wide association studies from bulk hippocampus, including GRM3 and CACNA1C. These results highlight the improved biological resolution provided by targeted sampling strategies like LCM and complement homogenate and single-nucleus approaches in human brain.
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