title: Genome-wide association of mood-incongruent psychotic bipolar disorder.
abstract: 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.
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. fgoes1@jhmi.edu
authors.forename: F S
authors.initials: FS
authors.lastname: Goes
authors.forename: M L
authors.initials: ML
authors.lastname: Hamshere
authors.forename: F
authors.initials: F
authors.lastname: Seifuddin
authors.forename: M
authors.initials: M
authors.lastname: Pirooznia
authors.forename: P
authors.initials: P
authors.lastname: Belmonte-Mahon
authors.forename: R
authors.initials: R
authors.lastname: Breuer
authors.forename: T
authors.initials: T
authors.lastname: Schulze
authors.forename: M
authors.initials: M
authors.lastname: Nöthen
authors.forename: S
authors.initials: S
authors.lastname: Cichon
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.forename: P
authors.initials: P
authors.lastname: Holmans
authors.forename: P P
authors.initials: PP
authors.lastname: Zandi
authors.forename: N
authors.initials: N
authors.lastname: Craddock
authors.forename: J B
authors.initials: JB
authors.lastname: Potash
mesh_terms: D000941:Antigens / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics; D057057:Serine Proteases / Q000235:genetics
chemical_list: D000941:Antigens; D008565:Membrane Proteins; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; C113026:NUMB protein, human; C439023:clathrin assembly protein AP180; C552271:PRSS35 protein, human; D057057:Serine Proteases