English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse
  1. View item / 
  2. Item Summary

Item

ITEM ACTIONSEXPORT
Add to Basket
  Local TagsRelease HistoryDetailsSummary

Released
Journal Article

Massively parallel functional dissection of schizophrenia- associated noncoding genetic variants

MPS-Authors
/persons/resource/persons262462

Rummel,  Christine
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons232551

Ahmad,  Ruhel
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons262308

Jiménez-Barrón,  Laura
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons276883

Murek,  Vanessa
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons294334

Weigert,  Liesa
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons294332

Hausruckinger,  Anna
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons294336

Maidl,  Susanne
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80355

Hauger,  Barbara
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons263179

Trastulla,  Lucia
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80315

Eder,  Matthias
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons203557

Ziller,  Michael J.
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Rummel, C., Gagliardi, M., Ahmad, R., Herholt, A., Jiménez-Barrón, L., Murek, V., et al. (2023). Massively parallel functional dissection of schizophrenia- associated noncoding genetic variants. CELL, 186(23), 5165-5182.e33. doi:10.1016/j.cell.2023.09.015.


Cite as: https://hdl.handle.net/21.11116/0000-000E-0DE5-2
Abstract
Schizophrenia (SCZ) is a highly heritable mental disorder with thousands of associated genetic variants located mostly in the noncoding space of the genome. Translating these associations into insights regarding the underlying pathomechanisms has been challenging because the causal variants, their mechanisms of ac-tion, and their target genes remain largely unknown. We implemented a massively parallel variant annotation pipeline (MVAP) to perform SCZ variant-to-function mapping at scale in disease-relevant neural cell types. This approach identified 620 functional variants (1.7%) that operate in a highly developmental context and neuronal-activity-dependent manner. Multimodal integration of epigenomic and CRISPRi screening data enabled us to link these functional variants to target genes, biological processes, and ultimately alterations of neuronal physiology. These results provide a multistage prioritization strategy to map functional single -nucleotide polymorphism (SNP)-to-gene-to-endophenotype relations and offer biological insights into the context-dependent molecular processes modulated by SCZ-associated genetic variation.