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Decoding causal m6A: a bioinformatics roadmap for psychiatric disorders.

Shuhe Liu^1,2,3, Xichen Zhao^1,3, Zhen Wei^1,2,4

¹Department of Biosciences and Bioinformatics, School of Science, Xi'an Jiaotong-Liverpool University, 111 Ren'ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.

Briefings in Bioinformatics

|May 25, 2026

Summary

This summary is machine-generated.

This review details bioinformatics methods to link N6-methyladenosine (m6A) RNA modifications to psychiatric disorders. These strategies help understand m6A's role in conditions like major depressive disorder.

Keywords:

causal inference m6A epitranscriptomics m6A-QTL mendelian randomization multi-omics integration psychiatric disorders

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Area of Science:

Neuroscience
Genetics
Bioinformatics

Background:

N6-methyladenosine (m6A) is a key RNA modification regulating gene expression in the central nervous system.
Dysregulation of m6A is implicated in psychiatric disorders, but causal links to disease phenotypes are unclear.

Purpose of the Study:

To provide a comprehensive survey of bioinformatics strategies for investigating m6A's role in psychiatric disorders.
To establish a roadmap for developing testable hypotheses for epitranscriptome-targeted therapies.

Main Methods:

The review outlines four analytical themes: false-positive signal calibration, causal inference using statistical genetics, cell-type-specific functional analysis, and machine learning for biomarker prediction.
Strategies were validated using a case study in major depressive disorder, intersecting m6A effects with psychiatric genetic risk.

Main Results:

The presented bioinformatics workflows enable the disentanglement of causal links between specific m6A sites and disease phenotypes.
The case study demonstrates the utility of these methods in understanding m6A's contribution to major depressive disorder.

Conclusions:

Streamlined bioinformatics approaches are crucial for advancing our understanding of the epitranscriptome in psychiatric disorders.
These methods pave the way for novel therapeutic interventions targeting m6A modifications.