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Isolating the Genetic Component of Mania in Bipolar Disorder
Giuseppe Pierpaolo Merola1, Johan Zvrskovec2, Rujia Wang2
1Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Psychiatry Unit, Department of Health Science, University of Florence, Florence, Italy.
Biological Psychiatry
|January 28, 2026
Summary
Researchers isolated the genetic component of mania in bipolar disorder using genomic structural equation modeling. This study identified 71 new genetic variants linked to mania, paving the way for targeted treatments.
Area of Science:
- Genetics
- Psychiatry
- Genomic Epidemiology
Background:
- Bipolar disorder involves mania, depression, and psychosis.
- Genetics of depression and psychosis are understood, but mania genetics remain underexplored.
- Understanding mania's genetic basis is crucial for bipolar disorder heterogeneity and targeted interventions.
Purpose of the Study:
- To isolate the genetic component specific to mania within bipolar disorder.
- To identify novel genetic loci associated with mania.
- To differentiate the genetic underpinnings of mania from depression.
Main Methods:
- Genomic structural equation modeling was employed.
- Genetic effects of major depressive disorder (MDD) were subtracted from bipolar disorder.
- Genome-wide association study (GWAS) summary statistics from large European ancestry cohorts were utilized.
Main Results:
- Mania explained 81.5% of bipolar disorder variance, while MDD explained 18.5%.
- Seventy-one independent significant single nucleotide polymorphisms (SNPs) associated with mania were identified across 37 genomic loci.
- Mania showed distinct genetic correlations with phenotypes like tiredness and educational attainment, and pathway analysis revealed enrichment in voltage-gated calcium channel activity.
Conclusions:
- The study provides a more bipolar disorder-specific GWAS by isolating mania-related genetic factors.
- Identification of mania-specific loci can aid in earlier diagnosis and personalized treatment strategies.
- Findings contribute to a deeper understanding of bipolar disorder's genetic architecture and may guide the development of novel therapies.
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