REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Anti-goat (donkey)	Thermo Fisher	Catalog # A21432, RRID: AB_2535853
Anti-guinea pig (goat)	Thermo Fisher	Catalog # A21450, RRID: AB_2535867
Anti-mouse (donkey)	Thermo Fisher	Catalog # A10037, RRID: AB_2534013
Anti-mouse (donkey)	Thermo Fisher	Catalog # A21202, RRID: AB_141607
Anti-rabbit (donkey)	Thermo Fisher	Catalog # A21206, RRID: AB_2535792
Anti-rabbit (donkey)	Thermo Fisher	Catalog # A10042, RRID: AB_2534017
Beta III tubulin (mouse)	Biolegend	Catalog # 801201, RRID: AB_2728521
Caspase-3 (rabbit)	Merck Millipore	Catalog # AB3623, RRID: AB_91556
ChAT (goat)	Merck Millipore	Catalog # AB144P, RRID: AB_2079751
Islet ½ (rabbit)	Abcam	Catalog # ab109517, RRID: AB_10866454
MAP-2 (guinea pig)	Synaptic systems	Catalog # 188004, RRID: AB_2138181
NeuN (mouse)	Merck Millipore	Catalog # MAB377, RRID: AB_2298772
Chemicals, peptides, and recombinant proteins
Acamprosate calcium	Sigma-Aldrich	Catalog # A6981
Accutase	StemCell Technologies	Catalog # 07922
All-trans retinoic acid	Merck Millipore	Catalog # 554720
B27 supplement	Thermo Fisher	Catalog # 17504044
Brain Derived Neurotrophic Factor (BDNF)	Peprotech	Catalog # 450-02
Camptothecin (CPT)	Cell Signaling Technology	Catalog # 13637
CHIR 99021	Tocris Biosciences	Catalog # 4423
Ciliary Neurotrophic Factor (CNTF)	Peprotech	Catalog # 450-13
Compound E	Merck Millipore	Catalog # 530509
D(−)-2-Amino-5-phosphonopentanoic acid (D-AP5)	Sigma-Aldrich	Catalog # A8054
4,6-diamidino-2-phenylindole (DAPI)	Merck Millipore	Catalog # 508741
Dimethyl Sulfoxide (DMSO)	Merck Millipore	Catalog # 317275
Distilled H2O	Merck Millipore	Catalog # EM3234
Dorsomorphin homolog 1 (DMH-1)	Tocris Biosciences	Catalog # 4126
GlutaMAX	Thermo Fisher	Catalog # 35050061
Hank’s balanced salt solution (HBSS)	Thermo Fisher	Catalog # 14175
Insulin-like Growth Factor-I (IGF-1)	Peprotech	Catalog # 100-11
KnockOut DMEM/F-12	Thermo Fisher	Catalog # A1370801
mTeSR Plus Basal Medium	StemCell Technologies	Catalog # 100-0276
N2 supplement	Thermo Fisher	Catalog # 17502048
Paraformaldehyde	Thermo Fisher	Catalog # 047392.9M
Penicillin/streptomycin	Merck Millipore	Catalog # 516106
Phosphate buffered saline (PBS)	Merck Millipore	Catalog # 6504
Purmorphamine (PMN)	Merck Millipore	Catalog # 540220
ReLeSR Passaging Reagent	StemCell Technologies	Catalog # 100-0484
Riluzole	Merck Millipore	Catalog # 557324
SB431542	Tocris Biosciences	Catalog # 1614
Triton X-100	Merck Millipore	Catalog # 648464
Vitronectin XF	StemCell Technologies	Catalog # 07180
Y27632 dihydrochloride	Tocris Biosciences	Catalog # 1254
Critical commercial assays
MTT assay	Thermo Fisher	Catalog #V13154
SNP beadchip genotyping array	Illumina	Catalog #: InfiniumOmni2-5-8v1-4_A1
Deposited data
ALS GWAS summary statistics	Van Rheenen et al.50	https://www.projectmine.com/research/download-data/
The individual-level data for the training and test datasets	Dewan et al.64	dbGaP (accession # phs001963.v1.p1), RRID: SCR_002709
The individual-level data for the training and test datasets	Nicolas et al.65	dbGaP (accession # phs000101.v5.p1), RRID: SCR_002709
The individual-level control data for the training and test datasets	https://dbgap.ncbi.nlm.nih.gov	dbGaP (accession # phs000001, phs000007, phs000187, phs000196, phs000292, phs000304, phs000315, phs000368, phs000372, phs000394, phs000397, phs000404, phs000421, phs000428, phs000615, phs000675, phs000801, and phs000869), RRID:SCR_002709
The individual-level data used as the replication dataset in this study.	King’s College London, unpublished study	Available from study principal investigator (Christopher Shaw, King’s College London) upon reasonable request.
The individual-level polygenic risk scores generated for the C9orf72 patients.	This study	https://zenodo.org/uploads/13769448
LINCS dataset	Subramanian et al.33	https://lincsproject.org, RRID: SCR_006454
The LINCS connectivity scores for the drugs evaluated as treatments for C9orf72-related disease.	This study	https://zenodo.org/records/13769483
RNA-sequencing data from the motor cortex	New York Genome Center	https://www.nygenome.org
RNA-sequencing data from the cerebellum	Prudencio et al.66	GEO (accession # GSE67196), RRID: SCR_005012
Experimental models: Cell lines
Human: iPS cell line	Cedars-Sinai	CS14iCTR-nxx
Human: iPS cell line	Coriell Biorepository	GM23338, RRID: CVCL_F182
Human: iPS cell line	University of Sheffield	MIFF1, RRID: CVCL_1E69
Human: iPS cell line	Cedars-Sinai	CS02iCTR-NTn1
Human: iPS cell line	University of Sheffield	ALS-183-C9
Human: iPS cell line	University of Sheffield	ALS-78
Human: iPS cell line	Cedars-Sinai	CS28iALS-C9nxx
Human: iPS cell line	Cedars-Sinai	CS29iALS-C9nxx
Human: iPS cell line	Cedars-Sinai	CS52iALS-C9nxx
Human: iPS cell line	Cedars-Sinai	CS29iALS-C9n1.ISOxx
Human: iPS cell line	Cedars-Sinai	CS52iALS-C9n6.ISOxx
Software and algorithms
Codes and scripts	This paper	https://github.com/sarasaezALS/C9orf72_AAO; https://zenodo.org/records/13259646
Drugmonizome	Kropiwnicki et al.34	https://maayanlab.cloud/drugmonizome/#/
ExperimentHub	https://www.bioconductor.org/packages/release/bioc/html/ExperimentHub.html	https://mrcieu.github.io/TwoSampleMR
Geneshot	Lachmann et al.30	https://maayanlab.cloud/genesgen, RRID: SCR_017582
g:Profiler2	Kolberg et al.29	https://biit.cs.ut.ee/gprofiler/ggos, RRID: SCR_018190
Harmony software	Perkin Elmer	Catalog # hh17000010, RRID: SCR_023543
PLINK (version 1.9)	PLINK Working Group	https://www.cog-genomics.org/plink/1.9/, RRID: SCR_001757
Prism (version 10)	GraphPad Software	https://www.graphpad.com, RRID: SCR_002798
PRSice2	Choi et al.67	https://choishingwan.github.ii/PRSice/, RRID: SCR_017057
Python	Python Team	https://www.python.org, RRID: SCR_008394
R (version 4.0.5)	R Core Team	https://www.r-project.org, RRID: SCR_001905
SignatureSearch (version 1.11.0)	Duan et al.68	https://bioconductor.org/packpack/release/bioc/vignettes/sigsignatureSea/inst/doc/signatursignatu.html, RRID: SCR_016177