TY - JOUR
T1 - Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes
AU - Ruderfer, Douglas M.
AU - Ripke, Stephan
AU - McQuillin, Andrew
AU - Boocock, James
AU - Stahl, Eli A.
AU - Pavlides, Jennifer M.Whitehead
AU - Mullins, Niamh
AU - Charney, Alexander W.
AU - Ori, Anil P.S.
AU - Loohuis, Loes M.Olde
AU - Domenici, Enrico
AU - Di Florio, Arianna
AU - Papiol, Sergi
AU - Kalman, Janos L.
AU - Trubetskoy, Vassily
AU - Adolfsson, Rolf
AU - Agartz, Ingrid
AU - Agerbo, Esben
AU - Akil, Huda
AU - Albani, Diego
AU - Albus, Margot
AU - Alda, Martin
AU - Alexander, Madeline
AU - Alliey-Rodriguez, Ney
AU - Als, Thomas D.
AU - Amin, Farooq
AU - Anjorin, Adebayo
AU - Arranz, Maria J.
AU - Awasthi, Swapnil
AU - Bacanu, Silviu A.
AU - Badner, Judith A.
AU - Baekvad-Hansen, Marie
AU - Bakker, Steven
AU - Band, Gavin
AU - Barchas, Jack D.
AU - Barroso, Ines
AU - Bass, Nicholas
AU - Bauer, Michael
AU - Baune, Bernhard T.
AU - Pedersen, Carsten Bocker
AU - Pedersen, Marianne Giortz
AU - Hansen, Mark
AU - Hansen, Thomas
AU - Li, Tao
AU - Nordentoft, Merete
AU - Olsen, Line
AU - Pers, Tune H.
AU - Rasmussen, Henrik B.
AU - Hansen, Christine Soholm
AU - Werge, Thomas
AU - Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium [email protected]
AU - Psychosis Endophenotypes International Consortium
AU - Wellcome Trust Case-Control Consortium
PY - 2018/6/14
Y1 - 2018/6/14
N2 - 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.
AB - 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.
KW - bipolar disorder
KW - polygenic risk
KW - psychosis
KW - schizophrenia
KW - subphenotypes
UR - http://www.scopus.com/inward/record.url?scp=85048172948&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2018.05.046
DO - 10.1016/j.cell.2018.05.046
M3 - Journal article
C2 - 29906448
AN - SCOPUS:85048172948
VL - 173
SP - 1705-1715.e16
JO - Cell
JF - Cell
SN - 0092-8674
IS - 7
ER -