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Publication Detail
Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Ruderfer DM, Ripke S, McQuillin A, Boocock J, Stahl EA, Pavlides JMW, Mullins N, Charney AW, Ori APS, Loohuis LMO, Domenici E, Di Florio A, Papiol S, Kalman JL, Trubetskoy V, Adolfsson R, Agartz I, Agerbo E, Akil H, Albani D, Albus M, Alda M, Alexander M, Alliey-Rodriguez N, Als TD, Amin F, Anjorin A, Arranz MJ, Awasthi S, Bacanu SA, Badner JA, Baekvad-Hansen M, Bakker S, Band G, Barchas JD, Barroso I, Bass N, Bauer M, Baune BT, Begemann M, Bellenguez C, Belliveau RA, Bellivier F, Bender S, Bene J, Bergen SE, Berrettini WH, Bevilacqua E, Biernacka JM, Bigdeli TB, Black DW, Blackburn H, Blackwell JM, Blackwood DHR, Pedersen CB, Boehnke M, Boks M, Borglum AD, Bramon E, Breen G, Brown MA, Bruggeman R, Buccola NG, Buckner RL, Budde M, Bulik-Sullivan B, Bumpstead SJ, Bunney W, Burmeister M, Buxbaum JD, Bybjerg-Grauholm J, Byerley W, Cahn W, Cai G, Cairns MJ, Campion D, Cantor RM, Carr VJ, Carrera N, Casas JP, Casas M, Catts SV, Cervantes P, Chambert KD, Chan RCK, Chen EYH, Chen RYL, Cheng W, Cheung EFC, Chong SA, Clarke TK, Cloninger CR, Cohen D, Cohen N, Coleman JRI, Collier DA, Cormican P, Coryell W, Craddock N, Craig DW
  • Publication date:
    14/06/2018
  • Journal:
    Cell
  • Status:
    Accepted
  • Print ISSN:
    0092-8674
Abstract
© 2018 Elsevier Inc. 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. 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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Division of Psychiatry
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Division of Psychiatry
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Genetics, Evolution & Environment
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Genetics, Evolution & Environment
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Division of Psychiatry
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Clinical and Movement Neurosciences
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