Adolescent multi-omics and Mendelian randomization reveal transdiagnostic molecular mechanisms in…

Cohort studyNature. Mental health· 2026

Adolescent multi-omics and Mendelian randomization reveal transdiagnostic molecular mechanisms in psychiatric disorders.

Luheng Qian, Runye Shi, Xinyang Yu … IMAGEN Consortium

Mood DisordersCohort studyQ1IF 5.4

Lower MRPL2 expression is causal for both insomnia and schizophrenia risk

Adolescent multi-omics and Mendelian randomization reveal transdiagnostic molecular mechanisms in psychiatric disorders.

Luheng Qian … IMAGEN Consortium

Nature. Mental health · 2026 · Q1 in Psychiatry

Background

The biological mechanisms underlying major neuropsychiatric disorders remain largely elusive.

Methods

Given the frequent association of immune dysregulation with these conditions, we used blood-derived multi-omics data from 1,274 healthy adolescents in the IMAGEN cohort to identify transdiagnostic biomarkers and mechanisms that could inform diagnosis and treatment.

n = 1,274 healthy adolescents

β = -0.38

Results

β = -0.38

Mendelian randomization estimate: lower MRPL2 expression linked to higher insomnia and schizophrenia risk

n = 1,274 healthy adolescents

More results

Two-step Mendelian randomization and colocalization analyses revealed potential transdiagnostic regulatory pathways, in which the expression of three genes ( MAD1L1 , MRPL2 and HLA-DRB1 ) mediated the effects of CpG methylation on schizophrenia and insomnia.

More results

Conversely, increased expression of MAD1L1 and HLA-DRB1 , driven by methylation at several CpG sites, was potentially causal for schizophrenia.

“

Conclusion

Our findings highlight key molecular mechanisms and genes implicated in neuropsychiatric disorders, offering promising new targets for therapeutic intervention.

Adolescent multi-omics and Mendelian randomization reveal transdiagnostic molecular mechanisms in psychiatric disorders.

Adolescent multi-omics and Mendelian randomization reveal transdiagnostic molecular mechanisms in psychiatric disorders.

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