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Genome-wide association of mood-incongruent psychotic bipolar disorder

Goes, F. S., Hamshere, Marian Lindsay ORCID:, Seifuddin, F., Pirooznia, M., Belmonte-Mahon, P., Breuer, R., Schulze, T., Nöthen, M., Cichon, S., Rietschel, M., Holmans, Peter Alan ORCID:, Zandi, P. P., Craddock, Nicholas John ORCID: and Potash, J. B. 2012. Genome-wide association of mood-incongruent psychotic bipolar disorder. Translational Psychiatry 2 (10) , e180. 10.1038/tp.2012.106

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Mood-incongruent psychotic features (MICP) are familial symptoms of bipolar disorder (BP) that also occur in schizophrenia (SZ), and may represent manifestations of shared etiology between the major psychoses. In this study we have analyzed three large samples of BP with imputed genome-wide association data and have performed a meta-analysis of 2196 cases with MICP and 8148 controls. We found several regions with suggestive evidence of association (P<10–6), although no marker met genome-wide significance criteria. The top associations were on chromosomes: 6q14.2 within the PRSS35/SNAP91 gene complex (rs1171113, P=9.67 × 10–8); 3p22.2 downstream of TRANK/LBA1 (rs9834970, P=9.71 × 10–8); and 14q24.2 in an intron of NUMB (rs2333194, P=7.03 × 10–7). These associations were present in all three samples, and both rs1171113 and rs2333194 were found to be overrepresented in an analysis of MICP cases compared with all other BP cases. To test the relationship of MICP with SZ, we performed polygenic analysis using the Psychiatric GWAS Consortium SZ results and found evidence of association between SZ polygenes and the presence of MICP in BP cases (meta-analysis P=0.003). In summary, our analysis of the MICP phenotype in BP has provided suggestive evidence for association of common variants in several genes expressed in the nervous system. The results of our polygenic analysis provides support for a modest degree of genetic overlap between BP with MICP and SZ, highlighting that phenotypic correlations across syndromes may be due to the influence of polygenic risk factors.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: bipolar disorder, genome-wide association study, psychosis, schizophrenia, SNAP91, TRANK1
Publisher: Nature Publishing Group
ISSN: 2158-3188
Last Modified: 21 Oct 2022 10:55

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