Heterogeneity analysis provides evidence for a genetically homogeneous subtype of bipolar-disorder
Our methodology has successfully identified a replicable homogeneous genetic subgroup of bipolar disorder. This subgroup may represent a collection of correlated genetic risk-factors for BDI. By investigating the subgroup's bicluster-informed polygenic-risk-scoring (PRS), we find that the disease-specific pattern highlighted by the bicluster can be leveraged to eliminate noise from our GWAS analyses and improve risk prediction. This improvement is particularly notable when using only a relatively small subset of the available SNPs, implying improved SNP replication. Though our primary focus is only the analysis of disease-related signal, we also identify replicable control-related heterogeneity.
Authors
- Caroline C. McGrouther
- John R. Kelsoe (ORCID: https://orcid.org/0000-0002-3013-2333)
- Jeremy A. Elman (ORCID: https://orcid.org/0000-0002-5840-1769)
- Arianna Di Florio (ORCID: https://orcid.org/0000-0003-0338-2748)
- Aaditya V. Rangan (ORCID: https://orcid.org/0000-0003-1579-7991)
- Nicholas J. Schork (ORCID: https://orcid.org/0000-0003-0920-5013)
Institutions
- Translational Genomics Research Institute (US)
- University of California San Diego (US)
- Courant Institute of Mathematical Sciences (US)
- New York University (US)
- Cardiff University (GB)
Publication Details
- Journal
- PLoS ONE
- Published
- 2025-01-29
- DOI
- https://doi.org/10.1371/journal.pone.0314288
- Citations
- 1
- Primary Topic
- Bipolar Disorder and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.47
Funders
- National Institutes of Health
- National Institute on Aging