RT Journal Article
T1 Association of polygenic score for major depression with response to lithium in patients with bipolar disorder.
A1 Amare, Azmeraw T
A1 Schubert, Klaus Oliver
A1 Hou, Liping
A1 Clark, Scott R
A1 Papiol, Sergi
A1 Cearns, Micah
A1 Heilbronner, Urs
A1 Degenhardt, Franziska
A1 Tekola-Ayele, Fasil
A1 Hsu, Yi-Hsiang
A1 Shekhtman, Tatyana
A1 Adli, Mazda
A1 Akula, Nirmala
A1 Akiyama, Kazufumi
A1 Ardau, Raffaella
A1 Arias, Bárbara
A1 Aubry, Jean-Michel
A1 Backlund, Lena
A1 Bhattacharjee, Abesh Kumar
A1 Bellivier, Frank
A1 Benabarre, Antonio
A1 Bengesser, Susanne
A1 Biernacka, Joanna M
A1 Birner, Armin
A1 Brichant-Petitjean, Clara
A1 Cervantes, Pablo
A1 Chen, Hsi-Chung
A1 Chillotti, Caterina
A1 Cichon, Sven
A1 Cruceanu, Cristiana
A1 Czerski, Piotr M
A1 Dalkner, Nina
A1 Dayer, Alexandre
A1 Del Zompo, Maria
A1 DePaulo, J Raymond
A1 Étain, Bruno
A1 Jamain, Stephane
A1 Falkai, Peter
A1 Forstner, Andreas J
A1 Frisen, Louise
A1 Frye, Mark A
A1 Fullerton, Janice M
A1 Gard, Sébastien
A1 Garnham, Julie S
A1 Goes, Fernando S
A1 Grigoroiu-Serbanescu, Maria
A1 Grof, Paul
A1 Hashimoto, Ryota
A1 Hauser, Joanna
A1 Herms, Stefan
A1 Hoffmann, Per
A1 Hofmann, Andrea
A1 Jiménez, Esther
A1 Kahn, Jean-Pierre
A1 Kassem, Layla
A1 Kuo, Po-Hsiu
A1 Kato, Tadafumi
A1 Kelsoe, John R
A1 Kittel-Schneider, Sarah
A1 Kliwicki, Sebastian
A1 König, Barbara
A1 Kusumi, Ichiro
A1 Laje, Gonzalo
A1 Landén, Mikael
A1 Lavebratt, Catharina
A1 Leboyer, Marion
A1 Leckband, Susan G
A1 Tortorella, Alfonso
A1 Manchia, Mirko
A1 Martinsson, Lina
A1 McCarthy, Michael J
A1 McElroy, Susan L
A1 Colom, Francesc
A1 Mitjans, Marina
A1 Mondimore, Francis M
A1 Monteleone, Palmiero
A1 Nievergelt, Caroline M
A1 Nöthen, Markus M
A1 Novák, Tomas
A1 O'Donovan, Claire
A1 Ozaki, Norio
A1 Ösby, Urban
A1 Pfennig, Andrea
A1 Potash, James B
A1 Reif, Andreas
A1 Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 
A1 Reininghaus, Eva
A1 Rouleau, Guy A
A1 Rybakowski, Janusz K
A1 Schalling, Martin
A1 Schofield, Peter R
A1 Schweizer, Barbara W
A1 Severino, Giovanni
A1 Shilling, Paul D
A1 Shimoda, Katzutaka
A1 Simhandl, Christian
A1 Slaney, Claire M
A1 Squassina, Alessio
A1 Stamm, Thomas
A1 Stopkova, Pavla
A1 Maj, Mario
A1 Turecki, Gustavo
A1 Vieta, Eduard
A1 Veeh, Julia
A1 Witt, Stephanie H
A1 Wright, Adam
A1 Zandi, Peter P
A1 Mitchell, Philip B
A1 Bauer, Michael
A1 Alda, Martin
A1 Rietschel, Marcella
A1 McMahon, Francis J
A1 Schulze, Thomas G
A1 Baune, Bernhard T
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.
YR 2020
FD 2020-03-16
LK https://hdl.handle.net/10668/25663
UL https://hdl.handle.net/10668/25663
LA en
DS RISalud
RD Apr 8, 2025