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  • Schubert, K. O. (author)

Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-11-29
  • Springer Science and Business Media LLC,2021

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/311270
  • https://gup.ub.gu.se/publication/311270URI
  • https://doi.org/10.1038/s41398-021-01702-2DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:148278631URI

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  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi(+)Gen; ). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.

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  • Thalamuthu, A. (author)
  • Amare, A. T. (author)
  • Frank, J. (author)
  • Streit, F. (author)
  • Adl, M. (author)
  • Akula, N. (author)
  • Akiyama, K. (author)
  • Ardau, R. (author)
  • Arias, B. (author)
  • Aubry, J. M. (author)
  • Backlund, L.Karolinska Institutet (author)
  • Bhattacharjee, A. K. (author)
  • Bellivier, F. (author)
  • Benabarre, A. (author)
  • Bengesser, S. (author)
  • Biernacka, J. M. (author)
  • Birner, A. (author)
  • Marie-Claire, C. (author)
  • Cearns, M. (author)
  • Cervantes, P. (author)
  • Chen, H. C. (author)
  • Chillotti, C.Karolinska Institutet (author)
  • Cichon, S. (author)
  • Clark, S. R. (author)
  • Cruceanu, C. (author)
  • Czerski, P. M. (author)
  • Dalkner, N. (author)
  • Dayer, A. (author)
  • Degenhardt, F. (author)
  • Del Zompo, M. (author)
  • DePaulo, J. R. (author)
  • Etain, B. (author)
  • Falkai, P. (author)
  • Forstner, A. J. (author)
  • Frisen, L.Karolinska Institutet (author)
  • Frye, M. A. (author)
  • Fullerton, J. M. (author)
  • Gard, S. (author)
  • Garnham, J. S. (author)
  • Goes, F. S. (author)
  • Grigoroiu-Serbanescu, M. (author)
  • Grof, P. (author)
  • Hashimoto, R. (author)
  • Hauser, J. (author)
  • Heilbronner, U. (author)
  • Herms, S. (author)
  • Hoffmann, P. (author)
  • Hou, L. P. (author)
  • Hsu, Y. H. (author)
  • Jamain, S. (author)
  • Jimenez, E. (author)
  • Kahn, J. P. (author)
  • Kassem, L. (author)
  • Kuo, P. H. (author)
  • Kato, T. (author)
  • Kelsoe, J. (author)
  • Kittel-Schneider, S. (author)
  • Ferensztajn-Rochowiak, E. (author)
  • Konig, B. (author)
  • Kusumi, I. (author)
  • Laje, G. (author)
  • Landén, Mikael,1966Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xlandt (author)
  • Lavebratt, C. (author)
  • Leboyer, M.Karolinska Institutet (author)
  • Leckband, S. G. (author)
  • Maj, M.Karolinska Institutet (author)
  • Manchia, M. (author)
  • Martinsson, L. (author)
  • McCarthy, M. J. (author)
  • McElroy, S. (author)
  • Colom, F. (author)
  • Mitjans, M. (author)
  • Mondimore, F. M. (author)
  • Monteleone, P. (author)
  • Nievergelt, C. M. (author)
  • Nothen, M. M. (author)
  • Novak, T. (author)
  • O'Donovan, C. (author)
  • Ozaki, N. (author)
  • Osby, U. (author)
  • Papiol, S. (author)
  • Pfennig, A. (author)
  • Pisanu, C. (author)
  • Potash, J. B. (author)
  • Reif, A. (author)
  • Reininghaus, E. (author)
  • Rouleau, G. A. (author)
  • Rybakowski, J. K. (author)
  • Schalling, M. (author)
  • Schofield, P. R. (author)
  • Schweizer, B. W. (author)
  • Severino, G. (author)
  • Shekhtman, T. (author)
  • Shilling, P. D. (author)
  • Shimoda, K. (author)
  • Simhandl, C. (author)
  • Slaney, C. M. (author)
  • Squassina, A. (author)
  • Stamm, T. (author)
  • Stopkova, P. (author)
  • Tekola-Ayele, F. (author)
  • Tortorella, A. (author)
  • Turecki, G. (author)
  • Veeh, J. (author)
  • Vieta, E. (author)
  • Witt, S. H. (author)
  • Roberts, G. (author)
  • Zandi, P. P. (author)
  • Alda, M. (author)
  • Bauer, M. (author)
  • McMahon, F. J. (author)
  • Mitchell, P. B. (author)
  • Schulze, T. G. (author)
  • Rietschel, M. (author)
  • Baune, B. T. (author)
  • Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi (creator_code:org_t)

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  • In:Translational Psychiatry: Springer Science and Business Media LLC11:12158-3188

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By the author/editor
Schubert, K. O.
Thalamuthu, A.
Amare, A. T.
Frank, J.
Streit, F.
Adl, M.
show more...
Akula, N.
Akiyama, K.
Ardau, R.
Arias, B.
Aubry, J. M.
Backlund, L.
Bhattacharjee, A ...
Bellivier, F.
Benabarre, A.
Bengesser, S.
Biernacka, J. M.
Birner, A.
Marie-Claire, C.
Cearns, M.
Cervantes, P.
Chen, H. C.
Chillotti, C.
Cichon, S.
Clark, S. R.
Cruceanu, C.
Czerski, P. M.
Dalkner, N.
Dayer, A.
Degenhardt, F.
Del Zompo, M.
DePaulo, J. R.
Etain, B.
Falkai, P.
Forstner, A. J.
Frisen, L.
Frye, M. A.
Fullerton, J. M.
Gard, S.
Garnham, J. S.
Goes, F. S.
Grigoroiu-Serban ...
Grof, P.
Hashimoto, R.
Hauser, J.
Heilbronner, U.
Herms, S.
Hoffmann, P.
Hou, L. P.
Hsu, Y. H.
Jamain, S.
Jimenez, E.
Kahn, J. P.
Kassem, L.
Kuo, P. H.
Kato, T.
Kelsoe, J.
Kittel-Schneider ...
Ferensztajn-Roch ...
Konig, B.
Kusumi, I.
Laje, G.
Landén, Mikael, ...
Lavebratt, C.
Leboyer, M.
Leckband, S. G.
Maj, M.
Manchia, M.
Martinsson, L.
McCarthy, M. J.
McElroy, S.
Colom, F.
Mitjans, M.
Mondimore, F. M.
Monteleone, P.
Nievergelt, C. M ...
Nothen, M. M.
Novak, T.
O'Donovan, C.
Ozaki, N.
Osby, U.
Papiol, S.
Pfennig, A.
Pisanu, C.
Potash, J. B.
Reif, A.
Reininghaus, E.
Rouleau, G. A.
Rybakowski, J. K ...
Schalling, M.
Schofield, P. R.
Schweizer, B. W.
Severino, G.
Shekhtman, T.
Shilling, P. D.
Shimoda, K.
Simhandl, C.
Slaney, C. M.
Squassina, A.
Stamm, T.
Stopkova, P.
Tekola-Ayele, F.
Tortorella, A.
Turecki, G.
Veeh, J.
Vieta, E.
Witt, S. H.
Roberts, G.
Zandi, P. P.
Alda, M.
Bauer, M.
McMahon, F. J.
Mitchell, P. B.
Schulze, T. G.
Rietschel, M.
Baune, B. T.
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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Psychiatry
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Neurology
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Translational Ps ...
By the university
University of Gothenburg
Karolinska Institutet

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