TY - JOUR
T1 - Genome-wide association study identifies 30 loci associated with bipolar disorder
AU - eQTLGen Consortium
AU - Stahl, Eli A
AU - Breen, Gerome
AU - Forstner, Andreas J
AU - McQuillin, Andrew
AU - Ripke, Stephan
AU - Trubetskoy, Vassily
AU - Mattheisen, Manuel
AU - Wang, Yunpeng
AU - Coleman, Jonathan R I
AU - Gaspar, Héléna A
AU - de Leeuw, Christiaan A
AU - Steinberg, Stacy
AU - Pavlides, Jennifer M Whitehead
AU - Trzaskowski, Maciej
AU - Byrne, Enda M
AU - Pers, Tune H
AU - Holmans, Peter A
AU - Richards, Alexander L
AU - Abbott, Liam
AU - Agerbo, Esben
AU - Akil, Huda
AU - Albani, Diego
AU - Alliey-Rodriguez, Ney
AU - Als, Thomas D
AU - Anjorin, Adebayo
AU - Antilla, Verneri
AU - Awasthi, Swapnil
AU - Badner, Judith A
AU - Bækvad-Hansen, Marie
AU - Barchas, Jack D
AU - Bass, Nicholas
AU - Bauer, Michael
AU - Belliveau, Richard
AU - Bergen, Sarah E
AU - Pedersen, Carsten Bøcker
AU - Bøen, Erlend
AU - Boks, Marco P
AU - Boocock, James
AU - Budde, Monika
AU - Bunney, William
AU - Burmeister, Margit
AU - Bybjerg-Grauholm, Jonas
AU - Byerley, William
AU - Casas, Miquel
AU - Cerrato, Felecia
AU - Cervantes, Pablo
AU - Chambert, Kimberly
AU - Charney, Alexander W
AU - Karlsson, Robert
AU - Stefansson, Kari
AU - Sigurðsson, Engilbert
PY - 2019/5
Y1 - 2019/5
N2 - Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.
AB - Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.
KW - Bipolar Disorder/classification
KW - Case-Control Studies
KW - Depressive Disorder, Major/genetics
KW - Female
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Psychotic Disorders/genetics
KW - Schizophrenia/genetics
KW - Systems Biology
U2 - 10.1038/s41588-019-0397-8
DO - 10.1038/s41588-019-0397-8
M3 - Article
C2 - 31043756
SN - 1061-4036
VL - 51
SP - 793
EP - 803
JO - Nature Genetics
JF - Nature Genetics
IS - 5
ER -