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Cell DOI:10.1016/j.cell.2018.05.046

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes.

Publication TypeJournal Article
Year of Publication2018
Corporate AuthorsBipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Electronic address: douglas.ruderfer@vanderbilt.edu, Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium
JournalCell
Volume173
Issue7
Pages1705-1715.e16
Date Published2018 06 14
ISSN1097-4172
KeywordsBipolar Disorder, Case-Control Studies, European Continental Ancestry Group, Genetic Loci, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Odds Ratio, Phenotype, Risk, Schizophrenia
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.

DOI10.1016/j.cell.2018.05.046
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29906448?dopt=Abstract

Alternate JournalCell
PubMed ID29906448
PubMed Central IDPMC6432650
Grant ListMR/M008436/1 / / Medical Research Council / United Kingdom
U01 MH109536 / MH / NIMH NIH HHS / United States
U01 MH109514 / MH / NIMH NIH HHS / United States
R01 MH111776 / MH / NIMH NIH HHS / United States
MR/L010305/1 / / Medical Research Council / United Kingdom