Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Knight, Jo (2018) Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. Cell, 173 (7). 1705-1715.e16. ISSN 0092-8674

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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 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.

Item Type:
Journal Article
Journal or Publication Title:
Cell
Additional Information:
This is the author’s version of a work that was accepted for publication in Cell. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cell, 173, 7, 2018 DOI: 10.1016/j.cell.2018.05.046
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300
Subjects:
ID Code:
126536
Deposited By:
Deposited On:
16 Aug 2018 08:14
Refereed?:
Yes
Published?:
Published
Last Modified:
23 Sep 2020 04:26