Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes
Ruderfer, Douglas M.; Ripke, Stephan; McQuillin, Andrew; Boocock, James; Stahl, Eli A.; Pavlides, Jennifer M.Whitehead; Mullins, Niamh; Charney, Alexander W.; Ori, Anil P.S.; Loohuis, Loes M.Olde; Domenici, Enrico; Di Florio, Arianna; Papiol, Sergi; Kalman, Janos L.; Trubetskoy, Vassily; Adolfsson, Rolf; Agartz, Ingrid; Agerbo, Esben; Akil, Huda; Albani, Diego; Albus, Margot; Alda, Martin; Alexander, Madeline; Alliey-Rodriguez, Ney; Als, Thomas D.; Amin, Farooq; Anjorin, Adebayo; Arranz, Maria J.; Awasthi, Swapnil; Bacanu, Silviu A.; Badner, Judith A.; Baekvad-Hansen, Marie; Bakker, Steven; Band, Gavin; Barchas, Jack D.; Barroso, Ines; Bass, Nicholas; Bauer, Michael; Baune, Bernhard T.; Begemann, Martin; Bellenguez, Celine; Belliveau, Richard A.; Bellivier, Frank; Bender, Stephan; Boks, Marco; Cahn, Wiepke; Kahn, Rene S.; Van Os, Jim; Strengman, Eric; Ophoff, Roel A.; Psychosis Endophenotypes International Consortium; Wellcome Trust Case Control Consortium; Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium douglas.ruderfer@vanderbilt.edu; Psychosis Endophenotypes International Consortium; Wellcome Trust Case Control Consortium
(2018) Cell, volume 173, issue 7, pp. 1705 - 1715.e16
(Article)
Abstract
Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114
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genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment. Genetic analysis of multiple bipolar disorder and schizophrenia cohorts reveals loci and polygenic risk scores that differentiate the clinical symptoms of these two highly correlated disorders.
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Keywords: Bipolar Disorder/genetics, Case-Control Studies, European Continental Ancestry Group/genetics, Genetic Loci, Genome-Wide Association Study, Humans, Multifactorial Inheritance/genetics, Odds Ratio, Phenotype, Risk, Schizophrenia/genetics, General Biochemistry,Genetics and Molecular Biology, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
ISSN: 0092-8674
Publisher: Cell Press
Note: Funding Information: The work of the contributing groups was supported by numerous grants from governmental and charitable bodies as well as philanthropic donation. Specifically, D.M.R. (R01MH111776) and N.R.W. (NHMRC 1078901, 1087889). Publisher Copyright: © 2018 Elsevier Inc.
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