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Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission

GSE263672 Homo sapiens (human) RNA-seq (gene expression) 14 samples Submitted 2024/05/06 Platform GPL16791

At a glance

RNA-seq (gene expression) · human · 14 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: 14 samples: 7 conditions, mostly in duplicateGroups 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: Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmissionMolecular psychiatry · 2024

Summary (written by the submitters)

Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. To address the question of how and when concordance in monozygotic twins occur, we have obtained fibroblasts from two pairs of schizophrenia discordant twins (one sibling with schizophrenia while the second one is unaffected by schizophrenia) and three pairs of healthy twins (both of the siblings are healthy).

Read the full summary ↓

We have prepared iPSC models for these 3 groups of patients with schizophrenia, unaffected co-twins, and the healthy twins. When the study started the co-twins were considered healthy and unaffected but both the co-twins were later diagnosed with a depressive disorder. The reprogrammed iPSCs were differentiated into hippocampal neurons to measure the neurophysiological abnormalities in the patients. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. Importantly, their synaptic activity was not affected. Our measurements that were obtained from schizophrenia patients and their monozygotic twin and compared also to control healthy twins point to hippocampal synaptic deficits as a central mechanism in schizophrenia

Published in

Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission

Stern S, Zhang L, Wang M et al. · Molecular psychiatry 2024 · PMID 38704507 · doi:10.1038/s41380-024-02561-1

This dataset

Open GSE263672 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 GSE263672_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 PRJNA1098725 and SRA study SRP501243. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38704507) ↗

Study design

7 conditions, mostly in duplicate

Control1 ×2 Control2 ×2 Control3 ×2 MZ_Patient1_clone ×2 MZ_Patient2_clone ×2 MZ_Cotwin1_clone ×2 MZ_Cotwin2_clone ×2

Supports a case/control comparison: 4 samples read as cases, 6 as controls.

How we read this: 7 replicated groups read from 14 sample titles; they account for 14 of them. 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

GSM8196339 Control1_1 Control1
GSM8196340 Control1_2 Control1
GSM8196341 Control2_1 Control2
GSM8196342 Control2_2 Control2
GSM8196343 Control3_1 Control3
GSM8196344 Control3_2 Control3
GSM8196345 MZ_Patient1_clone1 MZ_Patient1_clone
GSM8196346 MZ_Patient1_clone2 MZ_Patient1_clone
GSM8196347 MZ_Patient2_clone1 MZ_Patient2_clone
GSM8196348 MZ_Patient2_clone2 MZ_Patient2_clone
GSM8196349 MZ_Cotwin1_clone1 MZ_Cotwin1_clone
GSM8196350 MZ_Cotwin1_clone2 MZ_Cotwin1_clone
GSM8196351 MZ_Cotwin2_clone1 MZ_Cotwin2_clone
GSM8196352 MZ_Cotwin2_clone2 MZ_Cotwin2_clone

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GSE272752 Gain of bipolar disorder-related lncRNA AP1AR-DT in mice induces depressive and anxiety-like behaviors by reducing Negr1-mediated excitatory synaptic transmission [SK-N-SH RNA-seq] 4 samples shares transmission, synaptic

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