| Title: |
Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses |
| Authors: |
Panagiotaropoulou,Georgia; Hellberg,Kajsa-Lotta Georgii; Coleman,Jonathan R I; Seok,Darsol; Kalman,Janos; Mitchell,Philip B; Schofield,Peter R; Forstner,Andreas J; Bauer,Michael; Scott,Laura J; Pato,Carlos N; Pato,Michele T; Li,Qingqin S; Kirov,George; Landén,Mikael; Jonsson,Lina; Müller-Myhsok,Bertram; Smoller,Jordan W; Binder,Elisabeth B; Brückl,Tanja M; Czamara,Darina; Van der Auwera,Sandra; Grabe,Hans J; Homuth,Georg; Schmidt,Carsten O; Potash,James B; DePaulo,J Raymond; Goes,Fernando S; MacKinnon,Dean F; Mondimore,Francis M; Weissman,Myrna M; Shi,Jianxin; Frye,Mark A; Biernacka,Joanna M; Reif,Andreas; Witt,Stephanie H; Kahn, René R; Boks, Marco M; Owen,Michael J; Gordon-Smith,Katherine; Mitchell,Brittany L; Martin,Nicholas G; Medland,Sarah E; Jones,Lisa; Knowles,James A; Levinson,Douglas F; O'Donovan,Michael C; Lewis,Cathryn M; Breen,Gerome; Ophoff, Roel A; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Onderzoeksgroep 11; Onderzoek; Brain; Hersenen-Bedrijfsvoering |
| Publication Year: |
2025 |
| Subject Terms: |
Bipolar disorder; early differential diagnosis; genome-wide association analysis; major depressive disorder; polygenic risk scoring; Psychiatry and Mental health; Journal Article |
| Description: |
BACKGROUND: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD). AIMS: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis. METHOD: Based on individual genotypes from case-control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses. RESULTS: Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case-case GWAS and that of case-control BPD. CONCLUSIONS: We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text/plain |
| Language: |
English |
| ISSN: |
0007-1250 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/460254 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/460254 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.CF977DF0 |
| Database: |
BASE |