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Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

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Association of polygenic score for major depression with response to lithium in patients with bipolar disorder. / Amare, Azmeraw T; Schubert, Klaus Oliver; Hou, Liping et al.

In: Molecular Psychiatry, Vol. 26, No. 6, 06.2021, p. 2457-2470.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Amare, AT, Schubert, KO, Hou, L, Clark, SR, 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, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, H-C, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Étain, B, Jamain, S, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, 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

APA

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., ... 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, 26(6), 2457-2470. https://doi.org/10.1038/s41380-020-0689-5

CBE

Amare AT, Schubert KO, Hou L, Clark SR, Papiol S, Cearns M, Heilbronner U, Degenhardt F, Tekola-Ayele F, Hsu Y-H, et al. 2021. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder. Molecular Psychiatry. 26(6):2457-2470. https://doi.org/10.1038/s41380-020-0689-5

MLA

Vancouver

Amare AT, Schubert KO, Hou L, Clark SR, Papiol S, Cearns M et al. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder. Molecular Psychiatry. 2021 Jun;26(6):2457-2470. Epub 2020 Mar 16. doi: 10.1038/s41380-020-0689-5

Author

Amare, Azmeraw T ; Schubert, Klaus Oliver ; Hou, Liping et al. / Association of polygenic score for major depression with response to lithium in patients with bipolar disorder. In: Molecular Psychiatry. 2021 ; Vol. 26, No. 6. pp. 2457-2470.

Bibtex

@article{6d4082b124364720851ba67bd8028e86,
title = "Association of polygenic score for major depression with response to lithium in patients with bipolar disorder",
abstract = "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.",
keywords = "AGENTS, AUGMENTATION, EFFICACY, GENETICS, PHARMACOLOGICAL-TREATMENTS, POLARITY, PREDICTORS, PROPHYLACTIC LITHIUM, RISK, THERAPY",
author = "Amare, {Azmeraw T} and Schubert, {Klaus Oliver} and Liping Hou and Clark, {Scott R} and Sergi Papiol and Micah Cearns and Urs Heilbronner and Franziska Degenhardt and Fasil Tekola-Ayele and Yi-Hsiang Hsu and Tatyana Shekhtman and Mazda Adli and Nirmala Akula and Kazufumi Akiyama and Raffaella Ardau and B{\'a}rbara Arias and Jean-Michel Aubry and Lena Backlund and Bhattacharjee, {Abesh Kumar} and Frank Bellivier and Antonio Benabarre and Susanne Bengesser and Biernacka, {Joanna M} and Armin Birner and Clara Brichant-Petitjean and Pablo Cervantes and Hsi-Chung Chen and Caterina Chillotti and Sven Cichon and Cristiana Cruceanu and Czerski, {Piotr M} and Nina Dalkner and Alexandre Dayer and {Del Zompo}, Maria and DePaulo, {J Raymond} and Bruno {\'E}tain and Stephane Jamain and Peter Falkai and Forstner, {Andreas J} and Louise Frisen and Frye, {Mark A} and Fullerton, {Janice M} and S{\'e}bastien Gard and Garnham, {Julie S} and Goes, {Fernando S} and Maria Grigoroiu-Serbanescu and Paul Grof and Ryota Hashimoto and Joanna Hauser and Stefan Herms and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Mortensen, {Preben Bo} and Christensen, {Jane Hvarregaard}",
year = "2021",
month = jun,
doi = "10.1038/s41380-020-0689-5",
language = "English",
volume = "26",
pages = "2457--2470",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "6",

}

RIS

TY - JOUR

T1 - Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

AU - Amare, Azmeraw T

AU - Schubert, Klaus Oliver

AU - Hou, Liping

AU - Clark, Scott R

AU - Papiol, Sergi

AU - Cearns, Micah

AU - Heilbronner, Urs

AU - Degenhardt, Franziska

AU - Tekola-Ayele, Fasil

AU - Hsu, Yi-Hsiang

AU - Shekhtman, Tatyana

AU - Adli, Mazda

AU - Akula, Nirmala

AU - Akiyama, Kazufumi

AU - Ardau, Raffaella

AU - Arias, Bárbara

AU - Aubry, Jean-Michel

AU - Backlund, Lena

AU - Bhattacharjee, Abesh Kumar

AU - Bellivier, Frank

AU - Benabarre, Antonio

AU - Bengesser, Susanne

AU - Biernacka, Joanna M

AU - Birner, Armin

AU - Brichant-Petitjean, Clara

AU - Cervantes, Pablo

AU - Chen, Hsi-Chung

AU - Chillotti, Caterina

AU - Cichon, Sven

AU - Cruceanu, Cristiana

AU - Czerski, Piotr M

AU - Dalkner, Nina

AU - Dayer, Alexandre

AU - Del Zompo, Maria

AU - DePaulo, J Raymond

AU - Étain, Bruno

AU - Jamain, Stephane

AU - Falkai, Peter

AU - Forstner, Andreas J

AU - Frisen, Louise

AU - Frye, Mark A

AU - Fullerton, Janice M

AU - Gard, Sébastien

AU - Garnham, Julie S

AU - Goes, Fernando S

AU - Grigoroiu-Serbanescu, Maria

AU - Grof, Paul

AU - Hashimoto, Ryota

AU - Hauser, Joanna

AU - Herms, Stefan

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

AU - Mortensen, Preben Bo

AU - Christensen, Jane Hvarregaard

PY - 2021/6

Y1 - 2021/6

N2 - 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.

AB - 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.

KW - AGENTS

KW - AUGMENTATION

KW - EFFICACY

KW - GENETICS

KW - PHARMACOLOGICAL-TREATMENTS

KW - POLARITY

KW - PREDICTORS

KW - PROPHYLACTIC LITHIUM

KW - RISK

KW - THERAPY

UR - http://www.scopus.com/inward/record.url?scp=85081737215&partnerID=8YFLogxK

U2 - 10.1038/s41380-020-0689-5

DO - 10.1038/s41380-020-0689-5

M3 - Journal article

C2 - 32203155

VL - 26

SP - 2457

EP - 2470

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 6

ER -