Buchumschlag

Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach

Background - Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment. - - Aims - To use a combination of...

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Hauptverfasser: Cearns, Micah (VerfasserIn) , Amare, Azmeraw T. (VerfasserIn) , Schubert, Klaus Oliver (VerfasserIn) , Thalamuthu, Anbupalam (VerfasserIn) , Frank, Josef (VerfasserIn) , Streit, Fabian (VerfasserIn) , Adli, Mazda (VerfasserIn) , Akula, Nirmala (VerfasserIn) , Akiyama, Kazufumi (VerfasserIn) , Ardau, Raffaella (VerfasserIn) , Arias, Bárbara (VerfasserIn) , Aubry, Jean-Michel (VerfasserIn) , Backlund, Lena (VerfasserIn) , Bhattacharjee, Abesh Kumar (VerfasserIn) , Bellivier, Frank (VerfasserIn) , Benabarre, Antonio (VerfasserIn) , Bengesser, Susanne (VerfasserIn) , Biernacka, Joanna M. (VerfasserIn) , Birner, Armin (VerfasserIn) , Brichant-Petitjean, Clara (VerfasserIn) , Cervantes, Pablo (VerfasserIn) , Chen, Hsi-Chung (VerfasserIn) , Chillotti, Caterina (VerfasserIn) , Cichon, Sven (VerfasserIn) , Cruceanu, Cristiana (VerfasserIn) , Czerski, Piotr M. (VerfasserIn) , Dalkner, Nina (VerfasserIn) , Dayer, Alexandre (VerfasserIn) , Degenhardt, Franziska (VerfasserIn) , Zompo, Maria Del (VerfasserIn) , DePaulo, J. Raymond (VerfasserIn) , Étain, Bruno (VerfasserIn) , Falkai, Peter (VerfasserIn) , Forstner, Andreas J. (VerfasserIn) , Frisen, Louise (VerfasserIn) , Frye, Mark A. (VerfasserIn) , Fullerton, Janice M. (VerfasserIn) , Gard, Sébastien (VerfasserIn) , Garnham, Julie S. (VerfasserIn) , Goes, Fernando S. (VerfasserIn) , Grigoroiu-Serbanescu, Maria (VerfasserIn) , Grof, Paul (VerfasserIn) , Hashimoto, Ryota (VerfasserIn) , Hauser, Joanna (VerfasserIn) , Heilbronner, Urs (VerfasserIn) , Herms, Stefan (VerfasserIn) , Hoffmann, Per (VerfasserIn) , Hofmann, Andrea (VerfasserIn) , Hou, Liping (VerfasserIn) , Hsu, Yi-Hsiang (VerfasserIn) , Jamain, Stephane (VerfasserIn) , Jiménez, Esther (VerfasserIn) , Kahn, Jean-Pierre (VerfasserIn) , Kassem, Layla (VerfasserIn) , Kuo, Po-Hsiu (VerfasserIn) , Kato, Tadafumi (VerfasserIn) , Kelsoe, John (VerfasserIn) , Kittel-Schneider, Sarah (VerfasserIn) , Kliwicki, Sebastian (VerfasserIn) , König, Barbara (VerfasserIn) , Kusumi, Ichiro (VerfasserIn) , Laje, Gonzalo (VerfasserIn) , Landén, Mikael (VerfasserIn) , Lavebratt, Catharina (VerfasserIn) , Leboyer, Marion (VerfasserIn) , Leckband, Susan G. (VerfasserIn) , Maj, Mario (VerfasserIn) , Manchia, Mirko (VerfasserIn) , Martinsson, Lina (VerfasserIn) , McCarthy, Michael J. (VerfasserIn) , McElroy, Susan (VerfasserIn) , Colom, Francesc (VerfasserIn) , Mitjans, Marina (VerfasserIn) , Mondimore, Francis M. (VerfasserIn) , Monteleone, Palmiero (VerfasserIn) , Nievergelt, Caroline M. (VerfasserIn) , Nöthen, Markus M. (VerfasserIn) , Novák, Tomas (VerfasserIn) , O'Donovan, Claire (VerfasserIn) , Ozaki, Norio (VerfasserIn) , Millischer, Vincent (VerfasserIn) , Papiol, Sergi (VerfasserIn) , Pfennig, Andrea (VerfasserIn) , Pisanu, Claudia (VerfasserIn) , Potash, James B. (VerfasserIn) , Reif, Andreas (VerfasserIn) , Reininghaus, Eva (VerfasserIn) , Rouleau, Guy A. (VerfasserIn) , Rybakowski, Janusz K. (VerfasserIn) , Schalling, Martin (VerfasserIn) , Schofield, Peter R. (VerfasserIn) , Schweizer, Barbara W. (VerfasserIn) , Severino, Giovanni (VerfasserIn) , Shekhtman, Tatyana (VerfasserIn) , Shilling, Paul D. (VerfasserIn) , Shimoda, Katzutaka (VerfasserIn) , Simhandl, Christian (VerfasserIn) , Slaney, Claire M. (VerfasserIn) , Squassina, Alessio (VerfasserIn) , Stamm, Thomas (VerfasserIn) , Stopkova, Pavla (VerfasserIn) , Tekola-Ayele, Fasil (VerfasserIn) , Tortorella, Alfonso (VerfasserIn) , Turecki, Gustavo (VerfasserIn) , Veeh, Julia (VerfasserIn) , Vieta, Eduard (VerfasserIn) , Witt, Stephanie (VerfasserIn) , Roberts, Gloria (VerfasserIn) , Zandi, Peter P. (VerfasserIn) , Alda, Martin (VerfasserIn) , Bauer, Michael (VerfasserIn) , McMahon, Francis J. (VerfasserIn) , Mitchell, Philip B. (VerfasserIn) , Schulze, Thomas G. (VerfasserIn) , Rietschel, Marcella (VerfasserIn) , Clark, Scott R. (VerfasserIn) , Baune, Bernhard T. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 28 February 2022
In: The British journal of psychiatry
Year: 2022, Jahrgang: 220, Heft: 4, Pages: 219-228
ISSN:1472-1465
DOI:10.1192/bjp.2022.28
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1192/bjp.2022.28
Verlag, lizenzpflichtig, Volltext: http://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/using-polygenic-scores-and-clinical-data-for-bipolar-disorder-patient-stratification-and-lithium-response-prediction-machine-learning-approach/6AFF9E8BD7D3E7E086898EDB9522AAC1#
Volltext
Verfasserangaben:Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark and Bernhard T. Baune

MARC

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245 1 0 |a Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction  |b machine learning approach  |c Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark and Bernhard T. Baune 
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520 |a Background - Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment. - - Aims - To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder. - - Method - This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework. - - Results - The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data. - - Conclusions - Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment. 
650 4 |a bipolar affective disorders 
650 4 |a depressive disorders 
650 4 |a genetics 
650 4 |a Mood stabilisers 
650 4 |a outcome studies 
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JSO |a {"note":["In der Verfasserangabe im Artikel ist Frank, Josef fälschlich als \"Frank, Joseph\" geschrieben","Gesehen am 18.03.2024"],"title":[{"subtitle":"machine learning approach","title":"Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction","title_sort":"Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction"}],"person":[{"roleDisplay":"VerfasserIn","display":"Cearns, Micah","family":"Cearns","role":"aut","given":"Micah"},{"given":"Azmeraw T.","role":"aut","display":"Amare, Azmeraw T.","family":"Amare","roleDisplay":"VerfasserIn"},{"display":"Schubert, Klaus Oliver","family":"Schubert","roleDisplay":"VerfasserIn","given":"Klaus Oliver","role":"aut"},{"family":"Thalamuthu","display":"Thalamuthu, Anbupalam","roleDisplay":"VerfasserIn","role":"aut","given":"Anbupalam"},{"family":"Frank","display":"Frank, Josef","roleDisplay":"VerfasserIn","given":"Josef","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Streit, Fabian","family":"Streit","given":"Fabian","role":"aut"},{"roleDisplay":"VerfasserIn","family":"Adli","display":"Adli, Mazda","given":"Mazda","role":"aut"},{"given":"Nirmala","role":"aut","roleDisplay":"VerfasserIn","family":"Akula","display":"Akula, Nirmala"},{"role":"aut","given":"Kazufumi","family":"Akiyama","display":"Akiyama, Kazufumi","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","family":"Ardau","display":"Ardau, Raffaella","given":"Raffaella","role":"aut"},{"roleDisplay":"VerfasserIn","family":"Arias","display":"Arias, Bárbara","role":"aut","given":"Bárbara"},{"family":"Aubry","display":"Aubry, Jean-Michel","roleDisplay":"VerfasserIn","given":"Jean-Michel","role":"aut"},{"family":"Backlund","display":"Backlund, Lena","roleDisplay":"VerfasserIn","role":"aut","given":"Lena"},{"roleDisplay":"VerfasserIn","display":"Bhattacharjee, Abesh Kumar","family":"Bhattacharjee","given":"Abesh Kumar","role":"aut"},{"given":"Frank","role":"aut","family":"Bellivier","display":"Bellivier, Frank","roleDisplay":"VerfasserIn"},{"given":"Antonio","role":"aut","display":"Benabarre, Antonio","family":"Benabarre","roleDisplay":"VerfasserIn"},{"role":"aut","given":"Susanne","roleDisplay":"VerfasserIn","display":"Bengesser, Susanne","family":"Bengesser"},{"given":"Joanna M.","role":"aut","family":"Biernacka","display":"Biernacka, Joanna M.","roleDisplay":"VerfasserIn"},{"role":"aut","given":"Armin","roleDisplay":"VerfasserIn","display":"Birner, Armin","family":"Birner"},{"roleDisplay":"VerfasserIn","display":"Brichant-Petitjean, Clara","family":"Brichant-Petitjean","given":"Clara","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Cervantes, Pablo","family":"Cervantes","role":"aut","given":"Pablo"},{"role":"aut","given":"Hsi-Chung","family":"Chen","display":"Chen, Hsi-Chung","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","family":"Chillotti","display":"Chillotti, Caterina","role":"aut","given":"Caterina"},{"display":"Cichon, Sven","family":"Cichon","roleDisplay":"VerfasserIn","role":"aut","given":"Sven"},{"role":"aut","given":"Cristiana","roleDisplay":"VerfasserIn","family":"Cruceanu","display":"Cruceanu, Cristiana"},{"role":"aut","given":"Piotr M.","display":"Czerski, Piotr M.","family":"Czerski","roleDisplay":"VerfasserIn"},{"role":"aut","given":"Nina","family":"Dalkner","display":"Dalkner, Nina","roleDisplay":"VerfasserIn"},{"role":"aut","given":"Alexandre","display":"Dayer, Alexandre","family":"Dayer","roleDisplay":"VerfasserIn"},{"role":"aut","given":"Franziska","roleDisplay":"VerfasserIn","family":"Degenhardt","display":"Degenhardt, Franziska"},{"roleDisplay":"VerfasserIn","display":"Zompo, Maria Del","family":"Zompo","role":"aut","given":"Maria Del"},{"display":"DePaulo, J. 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SRT |a CEARNSMICAUSINGPOLYG2820 

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