GEO series

Massively parallel reporter assay investigates shared genetic variants of eight psychiatric disorders

GSE276947 Homo sapiens (human) RNA-seq (gene expression) 10 samples Submitted 2025/01/16 Platform GPL34281

At a glance

RNA-seq (gene expression) · human · 10 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 10 samples: 10 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Massively parallel reporter assay investigates shared genetic variants of eight psychiatric disordersCell · 2025

Summary (written by the submitters)

A meta-genome-wide association study across eight psychiatric disorders has shed light on the genetic architecture of pleiotropy in major psychiatric disorders. However, the mechanisms underlying pleiotropic effects of the associated variants remain to be investigated. We conducted a massively parallel reporter assay to decipher the regulatory logic of variants with disorder-specific and pleiotropic effects.

Read the full summary ↓

We found that pleiotropic variants differ from disorder-specific variants by manifesting chromatin accessibility that extends across diverse cell types in the neuronal lineage, as well as by altering motifs for transcription factors with higher connectivity in protein-protein interaction networks. Next, we mapped pleiotropic and disorder-specific variants to putative target genes using functional genomics approaches. CRISPR-mediated validation confirmed the functional impact of selected variants on predicted target genes. Furthermore, in vivo CRISPR perturbation of a pleiotropic and a disease-specific gene suggests that pleiotropy is mediated by the regulation of genes expressed in a broader range of neuronal types and with higher network connectivity.

Published in

Massively parallel reporter assay investigates shared genetic variants of eight psychiatric disorders

Lee S, McAfee JC, Lee J et al. · Cell 2025 · PMID 39848247 · doi:10.1016/j.cell.2024.12.022

This dataset

Open GSE276947 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE276947_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1159776 and SRA study SRP532113. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39848247) ↗

Study design

10 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 10 sample titles: 10 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8510239 iNeuron, replicate 1, scRNA-seq
GSM8510240 iNeuron, replicate 2, scRNA-seq
GSM8510241 iNeuron, replicate 3, scRNA-seq
GSM8510242 iNeuron, replicate 4, scRNA-seq
GSM8510243 iNeuron, replicate 5, scRNA-seq
GSM8510244 iNeuron, replicate 1, gRNA enrichment
GSM8510245 iNeuron, replicate 2, gRNA enrichment
GSM8510246 iNeuron, replicate 3, gRNA enrichment
GSM8510247 iNeuron, replicate 4, gRNA enrichment
GSM8510248 iNeuron, replicate 5, gRNA enrichment

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Search all human RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.