Study points to shared gene signals across six mental disorders

A new multi-omics study has identified three genes that appear to connect biological changes seen across several psychiatric, neurodevelopmental and sleep-related conditions. The findings matter because they point to molecular pathways that could help researchers study diagnosis and treatment across disorders that are usually examined separately.

The study, by Luheng Qian, Runye Shi and colleagues at Fudan University, King’s College London, University Paris-Saclay and other institutions, was published in Nature Mental Health. According to the authors, the biological causes of major neuropsychiatric disorders remain poorly understood, and immune-related disruption has often been associated with these conditions.

The researchers analyzed blood-derived biological data from 1,274 adolescents who had no diagnosed disease or mental health condition. The participants were part of the IMAGEN project, a European study examining how biological, psychological and environmental factors during adolescence relate to brain development and mental health risk.

Blood data used to trace molecular patterns

Qian, Shi and their colleagues used the IMAGEN data to look for genetic variants associated with DNA methylation and gene expression. DNA methylation involves chemical tags attaching to DNA, which can affect how strongly genes are switched on or off.

The team first ran genome-wide analyses to identify single nucleotide polymorphisms tied to methylation and expression patterns, then checked the findings in outside datasets, according to the paper. The researchers then used Mendelian randomization analyses across six conditions: attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia and insomnia.

The authors reported 73 putatively causal CpG sites and 62 genes that were either linked to individual disorders or shared across conditions. CpG sites are DNA regions where methylation can occur and influence gene activity.

The study highlighted three genes — MAD1L1, MRPL2 and HLA-DRB1 — as part of regulatory pathways linking methylation changes to disorder-related risk. The authors said these genes appeared to mediate molecular effects relevant to more than one condition.

Links to immune and psychiatric pathways

The identified genes were significantly enriched in pathways connected to psychiatric and autoimmune diseases, according to Qian, Shi and their colleagues. The authors said that pattern suggests shared genomic features between autoimmune and neuropsychiatric disorders.

More detailed analyses pointed to specific gene effects. The researchers reported that methylation at cg06770790 repressed MRPL2, and that this pattern was putatively causal for insomnia and schizophrenia. They also reported that increased expression of MAD1L1 and HLA-DRB1, driven by methylation at several CpG sites, was potentially causal for schizophrenia.

The paper does not show that these genes alone cause the disorders. Instead, the authors describe them as part of molecular mechanisms that could help explain shared biology across conditions with different symptoms and clinical features.

Qian, Shi and their colleagues said the findings identify genes and pathways that could become targets for therapeutic research. They also said the work could help guide future studies of biomarkers and molecular processes in disorders beyond those examined in this analysis.

Further research would be needed before the findings could be used in clinical diagnosis or treatment. For now, the study adds evidence that some psychiatric and neurodevelopmental conditions may share measurable biological signatures in blood-derived molecular data.

This story draws on original reporting from Medical Xpress.