Journal of Environmental Biology

Genetic and molecular insights into bipolar disorder: A genome-wide association study and bioinformatics analysis

J.P. Timmapuram¹*, G. Baby Shalini², T. Poojasree³, S. Vasishta⁴ and K. Farzia⁴     

¹Department of Psychiatry, Apollo Institute of Medical Sciences and Research Chittoor, Murukambattu - 517 127, India

²Department of OBG, Apollo Institute of Medical Sciences and Research Chittoor, Murukambattu - 517 127, India

³Department of Psychiatry, Apollo Institute of Medical Sciences and Research Chittoor, Murukambattu - 517 127, India

⁴Department of Biochemistry, Apollo Institute of Medical Sciences and Research Chittoor, Murukambattu - 517 127, India

Received: 29 November 2025                   Revised: 04 May 2026                   Accepted: 12 May 2026

*Corresponding Author Email: jayapriya_t@aimsrchittoor.edu.in                  *ORCiD: https://orcid.org/0009 0005 8604 6767

Abstract

Aim: Bipolar disorder is a multifactorial psychiatric condition characterized by mood dysregulation. Although its heritability is established, the underlying genetic mechanism still remains incomplete. Herein, the aim of this study was to integrate genome-wide association study data with functional analyses in order to nominate key genetic loci, and pathways and regulatory mechanisms involved in bipolar disorder.

Methodology: Public datasets for GWAS-identified bipolar disorder variants were downloaded and subjected to functional enrichment, protein-protein interaction mapping, and miRNA target prediction. The analyses focused on GO, Reactome, and KEGG pathway enrichment, as well as metabolomic and transcription factor analyses, to assess molecular dysregulation in bipolar disorder.

Results: Mitochondrial function, PALB2, RHOU; immune response, HLA-B, DPY19L3; synaptic signaling, KCNU1, DPP10; and metabolic processes. PPI analysis highlighted hub proteins such as PTK2 and PAK1, which might be regulatory proteins, while miRNA analysis revealed hsa-miR-126-3p and hsa-miR-452-5p as post-transcriptional regulators. Metabolomic assessment showed perturbations in GTP-binding proteins and magnesium homeostasis.

Interpretation: This integrative analysis enhances knowledge on the genetic and molecular architecture of bipolar disorder, reinforcing its polygenic nature and implicating mitochondrial dysfunction, immune dysregulation, and neurotransmitter imbalances. The identified pathways provide potential targets for therapeutic intervention, emphasizing the role of precision medicine in the management of bipolar disorder.

Key words: Bipolar disorder, GWAS, Bioinformatics, Genetic loci, Molecular mechanisms

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