Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.
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Panagiotaropoulou Georgia, Hellberg Kajsa-Lotta Georgii, Coleman Jonathan R I, Seok Darsol, Kalman Janos, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, iPSYCH Study Consortium, 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, Werge Thomas, Schork Andrew J, Ophoff Roel A, Ripke Stephan, Olde Loohuis Loes
Аннотация
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.