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Association of polygenic score for major depression with response to lithium in patients with bipolar disorder
AT. Amare, KO. Schubert, L. Hou, SR. Clark, S. Papiol, M. Cearns, U. Heilbronner, F. Degenhardt, F. Tekola-Ayele, YH. Hsu, T. Shekhtman, M. Adli, N. Akula, K. Akiyama, R. Ardau, B. Arias, JM. Aubry, L. Backlund, AK. Bhattacharjee, F. Bellivier,...
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, práce podpořená grantem
Grantová podpora
G0200243
Medical Research Council - United Kingdom
MR/L010305/1
Medical Research Council - United Kingdom
MR/L023784/2
Medical Research Council - United Kingdom
R01 MH059534
NIMH NIH HHS - United States
K02 DA021237
NIDA NIH HHS - United States
R01 MH059533
NIMH NIH HHS - United States
R01 MH060068
NIMH NIH HHS - United States
R01 MH059548
NIMH NIH HHS - United States
R01 MH059535
NIMH NIH HHS - United States
R01 MH059567
NIMH NIH HHS - United States
R01 MH059556
NIMH NIH HHS - United States
Z01 MH002810
Intramural NIH HHS - United States
64410
CIHR - Canada
NLK
ProQuest Central
od 2000-01-01 do Před 1 rokem
Open Access Digital Library
od 1997-01-01
Health & Medicine (ProQuest)
od 2000-01-01 do Před 1 rokem
Psychology Database (ProQuest)
od 2000-01-01 do Před 1 rokem
- MeSH
- bipolární porucha * farmakoterapie genetika MeSH
- celogenomová asociační studie MeSH
- deprese MeSH
- depresivní porucha unipolární * farmakoterapie genetika MeSH
- lidé MeSH
- lithium terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
Bipolar Center Wiener Neustadt Sigmund Freud University Medical Faculty Vienna Austria
Center for Molecular Medicine Karolinska University Hospital Stockholm Sweden
Centro de Investigación Biomédica en Red de Salud Mental Instituto de Salud Carlos 3 Madrid Spain
Clinical Neuroscience Max Planck Institute of Experimental Medicine Göttingen Germany
Department of Adult Psychiatry Poznan University of Medical Sciences Poznan Poland
Department of Biomedical Sciences University of Cagliari Cagliari Italy
Department of Clinical Neurosciences Karolinska Institutet Stockholm Sweden
Department of Health Sciences Research Mayo Clinic Rochester MN USA
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Mental Health Johns Hopkins Bloomberg School of Public Health Baltimore MD USA
Department of Molecular Medicine and Surgery Karolinska Institute Stockholm Sweden
Department of Pharmacology Dalhousie University Halifax NS Canada
Department of Psychiatry and Behavioral Sciences Johns Hopkins University Baltimore MD USA
Department of Psychiatry and Psychology Mayo Clinic Rochester MN USA
Department of Psychiatry and Psychotherapy Ludwig Maximilian University Munich Munich Germany
Department of Psychiatry and Psychotherapy University of Münster Münster Germany
Department of Psychiatry Dalhousie University Halifax NS Canada
Department of Psychiatry Dokkyo Medical University School of Medicine Mibu Tochigi Japan
Department of Psychiatry Hokkaido University Graduate School of Medicine Sapporo Japan
Department of Psychiatry Lindner Center of Hope University of Cincinnati Mason OH USA
Department of Psychiatry Melbourne Medical School University of Melbourne Parkville VIC Australia
Department of Psychiatry Mood Disorders Unit HUG Geneva University Hospitals Geneva Switzerland
Department of Psychiatry Osaka University Graduate School of Medicine Osaka Japan
Department of Psychiatry University of Basel Basel Switzerland
Department of Psychiatry University of California San Diego San Diego CA USA
Department of Psychiatry University of Campania Luigi Vanvitelli Naples Italy
Department of Psychiatry University of Perugia Perugia Italy
Department of Psychiatry VA San Diego Healthcare System San Diego CA USA
Discipline of Psychiatry School of Medicine University of Adelaide Adelaide SA Australia
Douglas Mental Health University Institute McGill University Montreal QC Canada
HSL Institute for Aging Research Harvard Medical School Boston MA USA
Human Genomics Research Group Department of Biomedicine University Hospital Basel Basel Switzerland
Inserm U955 Translational Psychiatry laboratory Fondation FondaMental Créteil France
Institute of Psychiatric Phenomics and Genomics University Hospital LMU Munich Munich Germany
Laboratory for Molecular Dynamics of Mental Disorders RIKEN Center for Brain Science Saitama Japan
Mental Health Research Group IMIM Hospital del Mar Barcelona Catalonia Spain
Montreal Neurological Institute and Hospital McGill University Montreal QC Canada
Mood Disorders Center of Ottawa Ottawa ON Canada
National Institute of Mental Health Klecany Czech Republic
Neuroscience Research Australia Sydney NSW Australia
Northern Adelaide Local Health Network Mental Health Services Adelaide SA Australia
Office of Mental Health VA San Diego Healthcare System San Diego CA USA
Program for Quantitative Genomics Harvard School of Public Health Boston MA USA
Psychiatric Genetic Unit Poznan University of Medical Sciences Poznan Poland
School of Medical Sciences University of New South Wales Sydney NSW Australia
School of Psychiatry University of New South Wales and Black Dog Institute Sydney NSW Australia
Service de psychiatrie Hôpital Charles Perrens Bordeaux France
The Neuromodulation Unit McGill University Health Centre Montreal QC Canada
Unit of Clinical Pharmacology Hospital University Agency of Cagliari Cagliari Italy
Unitat de Zoologia i Antropologia Biològica University of Barcelona CIBERSAM Barcelona Spain
Citace poskytuje Crossref.org
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- $a Association of polygenic score for major depression with response to lithium in patients with bipolar disorder / $c AT. Amare, KO. Schubert, L. Hou, SR. Clark, S. Papiol, M. Cearns, U. Heilbronner, F. Degenhardt, F. Tekola-Ayele, YH. Hsu, T. Shekhtman, M. Adli, N. Akula, K. Akiyama, R. Ardau, B. Arias, JM. Aubry, L. Backlund, AK. Bhattacharjee, F. Bellivier, A. Benabarre, S. Bengesser, JM. Biernacka, A. Birner, C. Brichant-Petitjean, P. Cervantes, HC. Chen, C. Chillotti, S. Cichon, C. Cruceanu, PM. Czerski, N. Dalkner, A. Dayer, M. Del Zompo, JR. DePaulo, B. Étain, S. Jamain, P. Falkai, AJ. Forstner, L. Frisen, MA. Frye, JM. Fullerton, S. Gard, JS. Garnham, FS. Goes, M. Grigoroiu-Serbanescu, P. Grof, R. Hashimoto, J. Hauser, S. Herms, P. Hoffmann, A. Hofmann, E. Jiménez, JP. Kahn, L. Kassem, PH. Kuo, T. Kato, JR. Kelsoe, S. Kittel-Schneider, S. Kliwicki, B. König, I. Kusumi, G. Laje, M. Landén, C. Lavebratt, M. Leboyer, SG. Leckband, A. Tortorella, M. Manchia, L. Martinsson, MJ. McCarthy, SL. McElroy, F. Colom, M. Mitjans, FM. Mondimore, P. Monteleone, CM. Nievergelt, MM. Nöthen, T. Novák, C. O'Donovan, N. Ozaki, U. Ösby, A. Pfennig, JB. Potash, A. Reif, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, E. Reininghaus, GA. Rouleau, JK. Rybakowski, M. Schalling, PR. Schofield, BW. Schweizer, G. Severino, PD. Shilling, K. Shimoda, C. Simhandl, CM. Slaney, A. Squassina, T. Stamm, P. Stopkova, M. Maj, G. Turecki, E. Vieta, J. Veeh, SH. Witt, A. Wright, PP. Zandi, PB. Mitchell, M. Bauer, M. Alda, M. Rietschel, FJ. McMahon, TG. Schulze, BT. Baune
- 520 9_
- $a Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
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