RT journal article
T1 Genetic identification of brain cell types underlying schizophrenia.
A1 Skene, N.G.
A1 Bryois, Julien
A1 Bakken, Trygve E.
A1 Breen, Gerome
A1 Crowley, James J.
A1 Gaspar, Héléna A.
A1 Giusti-Rodriguez, Paola
A1 Hodges, Rebecca D.
A1 Miller, Jeremy A.
A1 Muñoz Manchado, Ana Belén
A1 O’Donovan, Michael C.
A1 Owen, Michael J.
A1 Pardiñas, Antonio F.
A1 Ryge, J.
A1 Walters, James T. R
A1 Linnarsson, S.
A1 Lein, Ed S.
A1 Depressive, Major
A1 Disorder Working Group of the Psychiatric Genomics Consortium
A1 Sullivan, Patrick F.
A1 Hjerling-Leffler, Jens
A2 Anatomía PatológicaBiología Celular, Histología, Historia de la Ciencia, Medicina Legal y Forense y Toxicología
AB With few exceptions, the marked advances in knowledge about the genetic basis of schizophrenia have not converged on findings that can be confidently used for precise experimental modeling. By applying knowledge of the cellular taxonomy of the brain from single-cell RNA sequencing, we evaluated whether the genomic loci implicated in schizophrenia map onto specific brain cell types. We found that the common-variant genomic results consistently mapped to pyramidal cells, medium spiny neurons (MSNs) and certain interneurons, but far less consistently to embryonic, progenitor or glial cells. These enrichments were due to sets of genes that were specifically expressed in each of these cell types. We also found that many of the diverse gene sets previously associated with schizophrenia (genes involved in synaptic function, those encoding mRNAs that interact with FMRP, antipsychotic targets, etc.) generally implicated the same brain cell types. Our results suggest a parsimonious explanation: the common-variant genetic results for schizophrenia point at a limited set of neurons, and the gene sets point to the same cells. The genetic risk associated with MSNs did not overlap with that of glutamatergic pyramidal cells and interneurons, suggesting that different cell types have biologically distinct roles in schizophrenia.
SN 1546-1718
YR 2018
FD 2018
LK http://hdl.handle.net/10498/33469
UL http://hdl.handle.net/10498/33469
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 13-nov-2026