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| PMID |
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| TITLE |
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| Identifying genetic differences between bipolar disorder and major depression through multiple GWAS. |
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| ABSTRACT |
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| BACKGROUND |
NlmCategory: UNASSIGNED |
| Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). |
| AIMS |
NlmCategory: UNASSIGNED |
| Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. |
| METHODS |
NlmCategory: UNASSIGNED |
| Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. Based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting cohort of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform a variety of GWAS and polygenic risk scores (PRS) analyses. |
| RESULTS |
NlmCategory: UNASSIGNED |
| Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. Based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting cohort of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform a variety of GWAS and polygenic risk scores (PRS) analyses. While our GWAS is not well-powered to identify genome-wide significant loci, we find significant SNP-heritability and demonstrate the ability of the resulting PRS to distinguish BD from MDD, including BD cases with depressive onset. We replicate our PRS findings, but not signals of individual loci in an independent Danish cohort (iPSYCH 2015 case-cohort study, N=25,966). We observe strong genetic correlation between our case-case GWAS and that of case-control BD. |
| CONCLUSIONS |
NlmCategory: UNASSIGNED |
| Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. Based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting cohort of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform a variety of GWAS and polygenic risk scores (PRS) analyses. While our GWAS is not well-powered to identify genome-wide significant loci, we find significant SNP-heritability and demonstrate the ability of the resulting PRS to distinguish BD from MDD, including BD cases with depressive onset. We replicate our PRS findings, but not signals of individual loci in an independent Danish cohort (iPSYCH 2015 case-cohort study, N=25,966). We observe strong genetic correlation between our case-case GWAS and that of case-control BD. We find that MDD and BD, including BD with a depressive onset, are genetically distinct. Further, our findings support the hypothesis that Controls - MDD - BD primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BD and, importantly, BD with depressive onset from MDD. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| pubmed |
2024/02/27 06:44 |
| medline |
2024/02/27 06:45 |
| entrez |
2024/02/27 03:39 |
| pmc-release |
2024/02/26 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Panagiotaropoulou G |
|
Panagiotaropoulou |
Georgia |
G |
|
Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany. |
| Hellberg KG |
|
Hellberg |
Kajsa-Lotta Georgii |
KG |
|
Institute of Biological Psychiatry, Mental Health Center - Sct Hans, Copenhagen University Hospital, Copenhagen, Denmark. |
| Coleman JRI |
|
Coleman |
Jonathan R I |
JRI |
|
NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK. |
| Seok D |
|
Seok |
Darsol |
D |
|
Department of Psychiatry, University of California, Los Angeles, CA, USA. |
| Kalman J |
|
Kalman |
Janos |
J |
|
Institute for Psychiatric Phenomics and Genomics, Ludwig Maximilian University, Munich, Germany. |
|
Bipolar Disorder Working Group of the Psychiatric Genetics Consortium |
|
|
|
|
|
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Major Depressive Disorder Working Group of the Psychiatric Genetics Consortium |
|
|
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iPSYCH Study Consortium |
|
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| Mitchell PB |
|
Mitchell |
Philip B |
PB |
|
Discipline of Psychiatry and Mental Health, School of Medicine and Health, University of New South Wales, Sydney, Australia. |
| Schofield PR |
|
Schofield |
Peter R |
PR |
|
School of Biomedical Sciences, University of New South Wales, Sydney, University of New South Wales, Australia. |
| Forstner AJ |
|
Forstner |
Andreas J |
AJ |
|
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany. |
| Bauer M |
|
Bauer |
Michael |
M |
|
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany. |
| Scott LJ |
|
Scott |
Laura J |
LJ |
|
Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, MI, USA. |
| Pato CN |
|
Pato |
Carlos N |
CN |
|
Department of Psychiatry, Rutgers University, Rutgers Health, Piscataway, NJ, USA. |
| Pato MT |
|
Pato |
Michele T |
MT |
|
Department of Psychiatry, Rutgers University, Rutgers Health, Piscataway, NJ, USA. |
| Li QS |
|
Li |
Qingqin S |
QS |
|
Janssen Research and Development, Neuroscience, Titusville, NJ, USA. |
| Kirov G |
|
Kirov |
George |
G |
|
Cardiff University, Division of Psychological Medicine and Clinical Neuroscience, Cardiff, UK. |
| Landén M |
|
Landén |
Mikael |
M |
|
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| Jonsson L |
|
Jonsson |
Lina |
L |
|
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden. |
| Müller-Myhsok B |
|
Müller-Myhsok |
Bertram |
B |
|
Max Planck Institute of Psychiatry, Munich. |
| Smoller JW |
|
Smoller |
Jordan W |
JW |
|
Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. |
| Binder EB |
|
Binder |
Elisabeth B |
EB |
|
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich. |
| Brückl TM |
|
Brückl |
Tanja M |
TM |
|
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich. |
| Czamara D |
|
Czamara |
Darina |
D |
|
Department Genes and Environment, Max Planck Institute of Psychiatry, Munich. |
| der Auwera SV |
|
der Auwera |
Sandra Van |
SV |
|
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. |
| Grabe HJ |
|
Grabe |
Hans J |
HJ |
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Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. |
| Homuth G |
|
Homuth |
Georg |
G |
|
Interfaculty Institute of Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany. |
| Schmidt CO |
|
Schmidt |
Carsten O |
CO |
|
Institute for Community Medicine, Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany. |
| Potash JB |
|
Potash |
James B |
JB |
|
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. |
| DePaulo RJ |
|
DePaulo |
Raymond J |
RJ |
|
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. |
| Goes FS |
|
Goes |
Fernando S |
FS |
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Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. |
| MacKinnon DF |
|
MacKinnon |
Dean F |
DF |
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Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. |
| Mondimore FM |
|
Mondimore |
Francis M |
FM |
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Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. |
| Weissman MM |
|
Weissman |
Myrna M |
MM |
|
Division of Translational Epidemiology & Mental Health Equity, New York State Psychiatric Institute, New York, NY, US. |
| Shi J |
|
Shi |
Jianxin |
J |
|
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. |
| Frye MA |
|
Frye |
Mark A |
MA |
|
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. |
| Biernacka JM |
|
Biernacka |
Joanna M |
JM |
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Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA. |
| Reif A |
|
Reif |
Andreas |
A |
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Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany. |
| Witt SH |
|
Witt |
Stephanie H |
SH |
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Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. |
| Kahn RR |
|
Kahn |
René R |
RR |
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Department of Psychiatry and Behavioral Health System, Icahn School of Medicine at Mount Sinai, NY, USA. |
| Boks MM |
|
Boks |
Marco M |
MM |
|
Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands. |
| Owen MJ |
|
Owen |
Michael J |
MJ |
|
Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK. |
| Gordon-Smith K |
|
Gordon-Smith |
Katherine |
K |
|
Psychological Medicine, University of Worcester, Worcester, UK. |
| Mitchell BL |
|
Mitchell |
Brittany L |
BL |
|
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Medland SE |
|
Medland |
Sarah E |
SE |
|
Mental Health and Neuroscience, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Jones L |
|
Jones |
Lisa |
L |
|
Psychological Medicine, University of Worcester, Worcester, UK. |
| Knowles JA |
|
Knowles |
James A |
JA |
|
Department of Genetics, Rutgers University, Piscataway, NJ, US. |
| Levinson DF |
|
Levinson |
Douglas F |
DF |
|
Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, US. |
| O'Donovan MC |
|
O'Donovan |
Michael C |
MC |
|
Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK. |
| Lewis CM |
|
Lewis |
Cathryn M |
CM |
|
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK. |
| Breen G |
|
Breen |
Gerome |
G |
|
NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK. |
| Werge T |
|
Werge |
Thomas |
T |
|
Section for Geogenetics, GLOBE Institute, Faculty of Health and Medical Sciences, Copenhagen University. |
| Schork AJ |
|
Schork |
Andrew J |
AJ |
|
Institute of Biological Psychiatry, Mental Health Center - Sct Hans, Copenhagen University Hospital, Copenhagen, Denmark. |
| Ophoff R |
|
Ophoff |
Roel |
R |
|
Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. |
| Ripke S |
|
Ripke |
Stephan |
S |
|
German Center for Mental Health (DZPG), Site Berlin-Potsdam, Germany. |
| Loohuis LO |
|
Loohuis |
Loes Olde |
LO |
|
Department of Computational Medicine, University of California Los Angeles, Los Angeles, CA, USA. |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: medRxiv : the preprint server for health sciences |
| ISOABBREVIATION: medRxiv |
| YEAR: 2024 |
| MONTH: Jan |
| DAY: 30 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: |
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| MEDLINE JOURNAL |
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| MEDLINETA: medRxiv |
| COUNTRY: United States |
| ISSNLINKING: |
| NLMUNIQUEID: 101767986 |
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| PUBLICATIONTYPE TEXT |
| Preprint |
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