Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization.
The 9 matches
- [1] § Methods › Mendelian randomization between brain IDPs and DBs ↔ Part-3_Follow_up_analysis/6.1.putative causal DBs.DBToIDP.R, lines 81–142 · score 0.92 · Weighted median, Weighted mode, MR Egger, TwoSampleMR, putatively causal, ALS
- [2] § Methods › Mendelian randomization between brain IDPs and DBs ↔ Part-3_Follow_up_analysis/6.2.putative causal IDPs.IDPToDB.R, lines 82–143 · score 0.91 · Weighted median, Weighted mode, MR Egger, TwoSampleMR, putatively causal, ALS
- [3] § Methods › Primary Mendelian randomization analysis ↔ Part-3_Follow_up_analysis/4.1.replication rate in BrainMeta.R, lines 91–160 · score 0.72 · inverse variance weighted, Wald ratio, TwoSampleMR, IVW, exposure, pleiotropy
- [4] § Methods › Transcriptome-wide association study ↔ Part-1_TWAS/1.MetaXcan.R, lines 61–132 · score 0.64 · MetaXcan, brain tissue, V8, covariance, models, TWAS
- [5] § Methods › Gene set enrichment analysis ↔ Part-3_Follow_up_analysis/3.5.gene enrichment analysis.R, lines 61–113 · score 0.63 · clusterProfiler, enrichGO, enrichment, gene
- [6] § Results › Pervasive phenotype pleiotropy of causal eGenes ↔ Part-3_Follow_up_analysis/3.4.pLI score.R, lines 1–49 · score 0.59 · pLI scores, Behavioral cognitive phenotype, Brain regional volume, Neurological disorder, White matter microstructure, Psychiatric disorder
- [7] § Results › Pervasive phenotype pleiotropy of causal eGenes ↔ Part-3_Follow_up_analysis/3.4.pLI score.R, lines 1–49 · score 0.54 · pLI scores, brain regional volume, neurological disorder, behavioral cognitive, white matter microstructure, psychiatric
- [8] § Results › Pervasive phenotype pleiotropy of causal eGenes ↔ Part-3_Follow_up_analysis/3.4.pLI score.R, lines 51–106 · score 0.53 · pLI scores, brain regional volume, neurological disorder, white matter microstructure, psychiatric disorder
- [9] § Results › Shared cell type specificity of causal eGenes between different phenotype classes ↔ Part-3_Follow_up_analysis/6.3.putative routes.cell_type_eGene-DB-IDP.sankey plot.R, lines 108–185 · score 0.52 · DB IDP, inhibitory neuron, excitatory neurons, ASP, DPW, ADHD
Paper
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The authors' code
R · 224 lines · 12 KB · no license · 3 matches
3.4.pLI score.R at commit 9fe9e93, no license · at the source
Overview
- Department of Neurology, Zhongshan Hospital and Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
- College of Biomedical Engineering, Fudan University, Shanghai, China
- Department of Cardiovascular Medicine, RuiJin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang, China
- State Key Laboratory of Brain Function and Disorders, Institutes of Brain Science, Fudan University, Shanghai, China
- MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China
Abstract
Reconstructing causality routes from genetic effects to complex phenotypes in particular cell types is crucial for understanding biological mechanisms underlying the brain-associated phenotypes including imaging-derived phenotypes (IDPs), and brain disorders and behaviors (DBs). Here, we develop a single-cell Mendelian randomization framework to infer cell type-specific causal relationships between gene expression and diverse brain-associated complex phenotypes by integrating single-cell expression quantitative trait loci (cis-eQTLs) and genome-wide association study findings. We identifiy a set of 254 and 217 cis-eQTL target genes (eGenes) that may have causal effects on 112 IDPs and 26 DBs in eight cell types, respectively. These causal eGenes exhibit strong cell type specificity and varied pleiotropy among different types of brain-associated phenotypes. Further integrative analysis reveals putative causality routes among cell type-specific causal eGenes and brain-associated complex phenotypes. Finally, we characterize the spatiotemporal expression patterns of these causal eGenes, and highlight the coordinated associations of the brain-associated phenotypes based on the expression of their causal eGenes. Overall, our study presents a large-scale analysis of the genetic effects of brain structures, disorders and behaviors, providing a catalog of cell type-specific causal eGenes.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
Its files are read in the Code ↔ Paper reader above, with 9 matches between paragraphs and lines of code.
sldrcyang/ExpMR
9fe9e93936b4d08a14b07105fb43392e0765958e, 7 February 2026Availability: 1 check, the latest on 27 September 2026: the link answers
- 27 September 2026: the link answers
89 files, not copied: shown from their source
OSCR keeps no copy of these files: this repository has no license that allows it. The reader above shows each one from its source, fetched by your browser at commit 9fe9e93, when its fingerprint is the one OSCR verified. How this works.
- Part-1_TWAS/
1.MetaXcan.R — R, 244 lines, 1 match, shown from its source - Part-1_TWAS/
2.merge results.R — R, 136 lines, shown from its source - Part-2_MR_analysis/
GSMR/ — R, 23 lines, shown from its sourceBRVToDB.2.GSMR.format_ge nexp_data.R - Part-2_MR_analysis/
GSMR/ — R, 97 lines, shown from its sourceBRVToDB.3.GSMR.clumped.R - Part-2_MR_analysis/
GSMR/ — R, 129 lines, shown from its sourceBRVToDB.4.GSMR analysis.R - Part-2_MR_analysis/
GSMR/ — R, 78 lines, shown from its sourceCellToBRV.2.GSMR.format_ genexp_data.R - Part-2_MR_analysis/
GSMR/ — R, 50 lines, shown from its sourceCellToBRV.3.GSMR.format GWAS data.R - Part-2_MR_analysis/
GSMR/ — R, 125 lines, shown from its sourceCellToBRV.4.GSMR analysis.R - Part-2_MR_analysis/
GSMR/ — R, 127 lines, shown from its sourceCellToDB.4.GSMR analysis.R - Part-2_MR_analysis/
GSMR/ — R, 33 lines, shown from its sourceCellToWMMP.3.GSMR.format GWAS data.R - Part-2_MR_analysis/
GSMR/ — R, 127 lines, shown from its sourceCellToWMMP.4.GSMR analysis.R - Part-2_MR_analysis/
GSMR/ — R, 23 lines, shown from its sourceDBToBRV.2.GSMR.format_ge nexp_data.R - Part-2_MR_analysis/
GSMR/ — R, 81 lines, shown from its sourceDBToBRV.3.GSMR.clumped.R - Part-2_MR_analysis/
GSMR/ — R, 123 lines, shown from its sourceDBToBRV.4.GSMR analysis.R - Part-2_MR_analysis/
GSMR/ — R, 89 lines, shown from its sourceDBToWMMP.3.GSMR.clumped. R - Part-2_MR_analysis/
GSMR/ — R, 123 lines, shown from its sourceDBToWMMP.4.GSMR analysis.R - Part-2_MR_analysis/
GSMR/ — R, 24 lines, shown from its sourceWMMPToDB.2.GSMR.format_g enexp_data.R - Part-2_MR_analysis/
GSMR/ — R, 98 lines, shown from its sourceWMMPToDB.3.GSMR.clumped. R - Part-2_MR_analysis/
GSMR/ — R, 126 lines, shown from its sourceWMMPToDB.4.GSMR analysis.R - Part-2_MR_analysis/
PMR-Egger/ — R, 31 lines, shown from its sourceBRVToDB.1.PMR-Egger.form at_genexp_data.R - Part-2_MR_analysis/
PMR-Egger/ — R, 94 lines, shown from its sourceBRVToDB.2.PMR-Egger.clum ped.R - Part-2_MR_analysis/
PMR-Egger/ — R, 19 lines, shown from its sourceBRVToDB.3.generate xmat file.R - Part-2_MR_analysis/
PMR-Egger/ — R, 97 lines, shown from its sourceBRVToDB.4.PMR-Egger.R - Part-2_MR_analysis/
PMR-Egger/ — R, 65 lines, shown from its sourceCellToBRV.1.collate Malhotra lab data.R - Part-2_MR_analysis/
PMR-Egger/ — R, 29 lines, shown from its sourceCellToBRV.2.collate ukb_IDP data.R - Part-2_MR_analysis/
PMR-Egger/ — R, 74 lines, shown from its sourceCellToBRV.3.PMR-Egger.cl umped.R - Part-2_MR_analysis/
PMR-Egger/ — R, 17 lines, shown from its sourceCellToBRV.4.generate xmat file.R - Part-2_MR_analysis/
PMR-Egger/ — R, 90 lines, shown from its sourceCellToBRV.5.PMR-Egger.R - Part-2_MR_analysis/
PMR-Egger/ — R, 93 lines, shown from its sourceCellToDB.5.PMR-Egger.R - Part-2_MR_analysis/
PMR-Egger/ — R, 20 lines, shown from its sourceCellToWMMP.2.collate ukb_IDP data.R - Part-2_MR_analysis/
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PMR-Egger/ — R, 89 lines, shown from its sourceCellToWMMP.5.PMR-Egger.R - Part-2_MR_analysis/
PMR-Egger/ — R, 32 lines, shown from its sourceDBToBRV.1.PMR-Egger.form at_genexp_data.R - Part-2_MR_analysis/
PMR-Egger/ — R, 81 lines, shown from its sourceDBToBRV.2.PMR-Egger.clum ped.R - Part-2_MR_analysis/
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PMR-Egger/ — R, 94 lines, shown from its sourceDBToWMMP.4.PMR-Egger.R - Part-2_MR_analysis/
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PMR-Egger/ — R, 96 lines, shown from its sourceWMMPToDB.4.PMR-Egger.R - Part-2_MR_analysis/
SMR/ — R, 176 lines, shown from its sourceCellToBRV.1.SMR.generate matrixQTL file.R - Part-2_MR_analysis/
SMR/ — R, 48 lines, shown from its sourceCellToBRV.2.SMR.format GWAS data.R - Part-2_MR_analysis/
SMR/ — R, 37 lines, shown from its sourceCellToBRV.3.SMR.R - Part-2_MR_analysis/
SMR/ — R, 38 lines, shown from its sourceCellToDB.3.SMR.R - Part-2_MR_analysis/
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TwoSampleMR/ — R, 84 lines, shown from its sourceIDPToDB.3.TwoSampleMR.R - Part-3_Follow_up_analysi
s/ — R, 76 lines, shown from its source1.1.merge MR results.BRVToDB.R - Part-3_Follow_up_analysi
s/ — R, 169 lines, shown from its source1.2.merge MR results.CellToBRV.R - Part-3_Follow_up_analysi
s/ — R, 175 lines, shown from its source1.3.merge MR results.CellToDB.R - Part-3_Follow_up_analysi
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s/ — R, 86 lines, shown from its source1.7.merge MR results.WMMPToDB.R - Part-3_Follow_up_analysi
s/ — R, 216 lines, shown from its source2.1.putative causal eGenes.CellToDB.R - Part-3_Follow_up_analysi
s/ — R, 262 lines, shown from its source2.2.putative causal eGenes.CellToIDP.R - Part-3_Follow_up_analysi
s/ — R, 230 lines, shown from its source2.3.heatmap of causal eGenes.R - Part-3_Follow_up_analysi
s/ — R, 42 lines, shown from its source3.1.hypergeometric test for causal eGene overlap.R - Part-3_Follow_up_analysi
s/ — R, 156 lines, shown from its source3.2.bar chart and line chart for causal eGene overlap.R - Part-3_Follow_up_analysi
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s/ — R, 113 lines, 1 match, shown from its source3.5.gene enrichment analysis.R - Part-3_Follow_up_analysi
s/ — R, 195 lines, shown from its source3.6.heatmap of causal eGene ovelap.R - Part-3_Follow_up_analysi
s/ — R, 161 lines, 1 match, shown from its source4.1.replication rate in BrainMeta.R - Part-3_Follow_up_analysi
s/ — R, 75 lines, shown from its source4.2.replication rate in GWAS Catalog.R - Part-3_Follow_up_analysi
s/ — R, 68 lines, shown from its source4.3.replication rate in PhychEncode.R - Part-3_Follow_up_analysi
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s/ — R, 299 lines, shown from its source5.3.dumbbell chart.WMMP.R - Part-3_Follow_up_analysi
s/ — R, 200 lines, 1 match, shown from its source6.1.putative causal DBs.DBToIDP.R - Part-3_Follow_up_analysi
s/ — R, 202 lines, 1 match, shown from its source6.2.putative causal IDPs.IDPToDB.R - Part-3_Follow_up_analysi
s/ — R, 251 lines, 1 match, shown from its source6.3.putative routes.cell_type_eGene-D B-IDP.sankey plot.R - README.md — Text, 49 lines, shown from its source
The paper's code and data availability statement is in the Data section.
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Data
Datasets cited
- github.com/
laurahuckins/ — at github.com; found in “Data Availability”cmc_dlpfc_predixcan - zenodo:18584527 — at Zenodo; found in “Data Availability”
- zenodo:6104982 — at Zenodo; found in “Data Availability”
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The scripts in the study are publicly available via GitHub at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 12 MeSH terms, 5 funders, 167 references.
Cite
This paper
Yang, A., Zhao, X., Zhao, X.-M., & Yang, Y. T. (2026). Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization. PLoS computational biology, 22(6), e1014422. https://
BibTeX
@article{yang2026deciphe
author = {Yang, Anyi and Zhao, Xingzhong and Zhao, Xing-Ming and Yang, Yucheng T.},
title = {{Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization}},
journal = {PLoS computational biology},
year = {2026},
month = jun,
volume = {22},
number = {6},
pages = {e1014422},
publisher = {PLOS},
issn = {1553-734X},
doi = {10.1371/
url = {https://
pmid = {42308238},
pmcid = {PMC13289931}
}
RIS
TY - JOUR
AU - Yang, Anyi
AU - Zhao, Xingzhong
AU - Zhao, Xing-Ming
AU - Yang, Yucheng T.
TI - Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization
T2 - PLoS computational biology
J2 - PLoS Comput Biol
PY - 2026
DA - 2026/
VL - 22
IS - 6
SP - e1014422
SN - 1553-734X
PB - PLOS
DO - 10.1371/
UR - https://
LA - en
ER -
CSL-JSON
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