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Association of polygenic score for major depression with response to lithium in patients with bipolar disorder
- Source :
- Molecular Psychiatry, 26(6), 2457-2470. Nature Publishing Group, Amare, A T, Baune, B T, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Abdellaoui, A, Dolan, C V, Hottenga, J J, Mbarek, H, Middeldorp, C M, Nivard, M G, Willemsen, G, Boomsma, D I, de Geus, E J C, Beekman, A F T, Jansen, R, Milaneschi, Y, Peyrot, W J, Smit, J H, W J H Penninx, B & Posthuma, D 2021, ' Association of polygenic score for major depression with response to lithium in patients with bipolar disorder ', Molecular Psychiatry, vol. 26, no. 6, pp. 2457-2470 . https://doi.org/10.1038/s41380-020-0689-5, Amare, A T, Schubert, K O, Hou, L, Clark, S R, Papiol, S, Cearns, M, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, Y H, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J M, Backlund, L, Bhattacharjee, A K, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, J M, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, H C, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, P M, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, J R, Étain, B, Jamain, S, Falkai, P, Forstner, A J, Frisen, L, Frye, M A, Fullerton, J M, Nordentoft, M, Werge, T, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Wray, N R, Ripke, S, Matthiesen, M, Agerbo, E, Bækvad-Hansen, M, Buttenschøn, H N, Bybjerg-Grauholm, J, Grove, J, Hansen, C S, Hansen, T F, Hougaard, D M, Krogh, J, Pedersen, C B, Pedersen, M G, Qvist, P, Thompson, W K, Wang, Y, Weinsheimer, S M, Mortensen, P B, Christensen, J V & Børglum, A D 2021, ' Association of polygenic score for major depression with response to lithium in patients with bipolar disorder ', Molecular Psychiatry, vol. 26, pp. 2457–2470 . https://doi.org/10.1038/s41380-020-0689-5, Molecular psychiatry 26(6), 2457-2470 (2021). doi:10.1038/s41380-020-0689-5, Molecular Psychiatry, Molecular Psychiatry, 2021, Online ahead of print. ⟨10.1038/s41380-020-0689-5⟩, Amare, A T, Schubert, K O, Hou, L, Clark, S R, Papiol, S, Cearns, M, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, Y H, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J M, Backlund, L, Bhattacharjee, A K, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, J M, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, H C, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, P M, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, J R, Étain, B, Jamain, S, Falkai, P, Forstner, A J, Frisen, L, Frye, M A, Fullerton, J M, Gard, S, Garnham, J S, Goes, F S, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Hofmann, A, Jiménez, E, Kahn, J P, Kassem, L, Kuo, P H, Kato, T, Kelsoe, J R, Kittel-Schneider, S, Kliwicki, S, König, B, Kusumi, I, Laje, G, Landén, M, Lavebratt, C, Leboyer, M, Leckband, S G, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, M J, McElroy, S L, Colom, F, Mitjans, M, Mondimore, F M, Monteleone, P, Nievergelt, C M, Nöthen, M M, Novák, T, O’Donovan, C, Ozaki, N, Ösby, U, Pfennig, A, Potash, J B, Reif, A, Wray, N R, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, E M, Abdellaoui, A, Adams, M J, Agerbo, E, Air, T M, Andlauer, T F M, Bacanu, S A, Bækvad-Hansen, M, Beekman, A T F, Bigdeli, T B, Binder, E B, Blackwood, D H R, Bryois, J, Buttenschøn, H N, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, J V, Clarke, T K, Coleman, J R I, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, G E, Davies, G, Deary, I J, Degenhardt, F, Derks, E M, Direk, N, Dolan, C V, Dunn, E C, Eley, T C, Escott-Price, V, Kiadeh, F F H, Finucane, H K, Forstner, A J, Frank, J, Gaspar, H A, Gill, M, Goes, F S, Gordon, S D, Grove, J, Hall, L S, Hansen, C S, Hansen, T F, Herms, S, Hickie, I B, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J J, Hougaard, D M, Ising, M, Jansen, R, Jorgenson, E, Knowles, J A, Kohane, I S, Kraft, J, Kretzschmar, W W, Krogh, J, Kutalik, Z, Li, Y, Lind, P A, MacIntyre, D J, MacKinnon, D F, Maier, R M, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, S E, Mehta, D, Middeldorp, C M, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, F M, Montgomery, G W, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, M G, Nyholt, D R, O’Reilly, P F, Oskarsson, H, Owen, M J, Painter, J N, Pedersen, C B, Pedersen, M G, Peterson, R E, Pettersson, E, Peyrot, W J, Pistis, G, Posthuma, D, Quiroz, J A, Qvist, P, Rice, J P, Riley, B P, Rivera, M, Mirza, S S, Schoevers, R, Schulte, E C, Shen, L, Shi, J, Shyn, S I, Sigurdsson, E, Sinnamon, G C B, Smit, J H, Smith, D J, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, K E, Teismann, H, Teumer, A, Thompson, W, Thomson, P A, Thorgeirsson, T E, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, A G, Umbricht, D, Van der Auwera, S, van Hemert, A M, Viktorin, A, Visscher, P M, Wang, Y, Webb, B T, Weinsheimer, S M, Wellmann, J, Willemsen, G, Witt, S H, Wu, Y, Xi, H S, Yang, J, Zhang, F, Arolt, V, Baune, B T, Berger, K, Boomsma, D I, Cichon, S, Dannlowski, U, de Geus, E J C, DePaulo, J R, Domenici, E, Domschke, K, Esko, T, Grabe, H J, Hamilton, S P, Hayward, C, Heath, A C, Kendler, K S, Kloiber, S, Lewis, G, Li, Q S, Lucae, S, Madden, P A F, Magnusson, P K, Martin, N G, McIntosh, A M, Metspalu, A, Mors, O, Mortensen, P B, Müller-Myhsok, B, Nordentoft, M, Nöthen, M M, O’Donovan, M C, Paciga, S A, Pedersen, N L, Penninx, B W J H, Perlis, R H, Porteous, D J, Potash, J B, Preisig, M, Rietschel, M, Schaefer, C, Schulze, T G, Smoller, J W, Stefansson, K, Tiemeier, H, Uher, R, Völzke, H, Weissman, M M, Werge, T, Lewis, C M, Levinson, D F, Breen, G, Børglum, A D, Sullivan, P F, Reininghaus, E, Rouleau, G A, Rybakowski, J K, Schalling, M, Schofield, P R, Schweizer, B W, Severino, G, Shilling, P D, Shimoda, K, Simhandl, C, Slaney, C M, Squassina, A, Stamm, T, Stopkova, P, Maj, M, Turecki, G, Vieta, E, Veeh, J, Witt, S H, Wright, A, Zandi, P P, Mitchell, P B, Bauer, M, Alda, M, Rietschel, M, McMahon, F J, Schulze, T G, Baune, B T & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2021, ' Association of polygenic score for major depression with response to lithium in patients with bipolar disorder ', Molecular Psychiatry, vol. 26, no. 6, pp. 2457-2470 . https://doi.org/10.1038/s41380-020-0689-5, Amare, A T, Schubert, K O, Hou, L, Clark, S R, Papiol, S, Cearns, M, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, Y-H, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J-M, Backlund, L, Bhattacharjee, A K, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, J M, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, H-C, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, P M, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, J R, Étain, B, Jamain, S, Falkai, P, Forstner, A J, Frisen, L, Frye, M A, Fullerton, J M, Gard, S, Garnham, J S, Goes, F S, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2021, ' Association of polygenic score for major depression with response to lithium in patients with bipolar disorder ', Molecular Psychiatry, vol. 26, no. 6, pp. 2457-2470 . https://doi.org/10.1038/s41380-020-0689-5, Molecular Psychiatry, Nature Publishing Group, 2021, Online ahead of print. ⟨10.1038/s41380-020-0689-5⟩, Molecular Psychiatry (2020), Molecular psychiatry, 26(6), 2457-2470. Nature Publishing Group
- Publication Year :
- 2021
-
Abstract
- © 2020, The Author(s), under exclusive licence to Springer Nature Limited.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.
- Subjects :
- 0301 basic medicine
Netherlands Twin Register (NTR)
Lithium (medication)
[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health
Genome-wide association study
Logistic regression
THERAPY
ddc:616.89
0302 clinical medicine
Medicine
Major depression
PREDICTORS
Depression (differential diagnoses)
RISK
Depression
Psychiatry and Mental health
Quartile
Cohort
AUGMENTATION
medicine.drug
POLARITY
medicine.medical_specialty
GENETICS
Bipolar disorder
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Lithium
PROPHYLACTIC LITHIUM
03 medical and health sciences
Cellular and Molecular Neuroscience
SDG 3 - Good Health and Well-being
Internal medicine
Humans
ddc:610
AGENTS
Molecular Biology
Genetic association
Depressive Disorder, Major
business.industry
medicine.disease
EFFICACY
030104 developmental biology
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health
PHARMACOLOGICAL-TREATMENTS
business
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 13594184 and 14765578
- Volume :
- 26
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Molecular psychiatry
- Accession number :
- edsair.doi.dedup.....edcaa7338db07c72a64e32d0cc9bef51
- Full Text :
- https://doi.org/10.1038/s41380-020-0689-5