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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

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@article{20dd05f194b444aeace89ba3b084fcfa,
title = "Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology",
abstract = "Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.",
keywords = "Bipolar Disorder/genetics, Case-Control Studies, Chromosomes, Human/genetics, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Major Histocompatibility Complex/genetics, Multifactorial Inheritance/genetics, Phenotype, Quantitative Trait Loci/genetics, Risk Factors",
author = "Niamh Mullins and Forstner, {Andreas J} and O'Connell, {Kevin S} and Brandon Coombes and Coleman, {Jonathan R I} and Zhen Qiao and Als, {Thomas D} and Bigdeli, {Tim B} and Sigrid B{\o}rte and Julien Bryois and Charney, {Alexander W} and Drange, {Ole Kristian} and Gandal, {Michael J} and Hagenaars, {Saskia P} and Masashi Ikeda and Nolan Kamitaki and Minsoo Kim and Kristi Krebs and Georgia Panagiotaropoulou and Schilder, {Brian M} and Sloofman, {Laura G} and Stacy Steinberg and Vassily Trubetskoy and Winsvold, {Bendik S} and Hong-Hee Won and Liliya Abramova and Kristina Adorjan and Esben Agerbo and {Al Eissa}, Mariam and Diego Albani and Ney Alliey-Rodriguez and Adebayo Anjorin and Verneri Antilla and Anastasia Antoniou and Swapnil Awasthi and Baek, {Ji Hyun} and Marie B{\ae}kvad-Hansen and Nicholas Bass and Michael Bauer and Beins, {Eva C} and Bergen, {Sarah E} and Armin Birner and {B{\o}cker Pedersen}, Carsten and Erlend B{\o}en and Boks, {Marco P} and Rosa Bosch and Murielle Brum and Brumpton, {Ben M} and Merete Nordentoft and Thomas Werge and {HUNT All-In Psychiatry}",
year = "2021",
month = jun,
doi = "10.1038/s41588-021-00857-4",
language = "English",
volume = "53",
pages = "817--829",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "6",

}

RIS

TY - JOUR

T1 - Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

AU - Mullins, Niamh

AU - Forstner, Andreas J

AU - O'Connell, Kevin S

AU - Coombes, Brandon

AU - Coleman, Jonathan R I

AU - Qiao, Zhen

AU - Als, Thomas D

AU - Bigdeli, Tim B

AU - Børte, Sigrid

AU - Bryois, Julien

AU - Charney, Alexander W

AU - Drange, Ole Kristian

AU - Gandal, Michael J

AU - Hagenaars, Saskia P

AU - Ikeda, Masashi

AU - Kamitaki, Nolan

AU - Kim, Minsoo

AU - Krebs, Kristi

AU - Panagiotaropoulou, Georgia

AU - Schilder, Brian M

AU - Sloofman, Laura G

AU - Steinberg, Stacy

AU - Trubetskoy, Vassily

AU - Winsvold, Bendik S

AU - Won, Hong-Hee

AU - Abramova, Liliya

AU - Adorjan, Kristina

AU - Agerbo, Esben

AU - Al Eissa, Mariam

AU - Albani, Diego

AU - Alliey-Rodriguez, Ney

AU - Anjorin, Adebayo

AU - Antilla, Verneri

AU - Antoniou, Anastasia

AU - Awasthi, Swapnil

AU - Baek, Ji Hyun

AU - Bækvad-Hansen, Marie

AU - Bass, Nicholas

AU - Bauer, Michael

AU - Beins, Eva C

AU - Bergen, Sarah E

AU - Birner, Armin

AU - Bøcker Pedersen, Carsten

AU - Bøen, Erlend

AU - Boks, Marco P

AU - Bosch, Rosa

AU - Brum, Murielle

AU - Brumpton, Ben M

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - HUNT All-In Psychiatry

PY - 2021/6

Y1 - 2021/6

N2 - Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

AB - Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

KW - Bipolar Disorder/genetics

KW - Case-Control Studies

KW - Chromosomes, Human/genetics

KW - Genetic Predisposition to Disease

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Humans

KW - Major Histocompatibility Complex/genetics

KW - Multifactorial Inheritance/genetics

KW - Phenotype

KW - Quantitative Trait Loci/genetics

KW - Risk Factors

UR - http://www.scopus.com/inward/record.url?scp=85107422437&partnerID=8YFLogxK

U2 - 10.1038/s41588-021-00857-4

DO - 10.1038/s41588-021-00857-4

M3 - Journal article

C2 - 34002096

VL - 53

SP - 817

EP - 829

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 6

ER -

ID: 65785482