| Literature DB >> 32203155 |
Azmeraw T Amare1,2, Klaus Oliver Schubert1,3, Liping Hou4, Scott R Clark1, Sergi Papiol5,6, Micah Cearns1, Urs Heilbronner5,7, Franziska Degenhardt8, Fasil Tekola-Ayele9, Yi-Hsiang Hsu10,11, Tatyana Shekhtman12, Mazda Adli13, Nirmala Akula4, Kazufumi Akiyama14, Raffaella Ardau15, Bárbara Arias16, Jean-Michel Aubry17, Lena Backlund18,19, Abesh Kumar Bhattacharjee12, Frank Bellivier20, Antonio Benabarre21, Susanne Bengesser22, Joanna M Biernacka23,24, Armin Birner22, Clara Brichant-Petitjean20, Pablo Cervantes25, Hsi-Chung Chen26, Caterina Chillotti15, Sven Cichon8,27, Cristiana Cruceanu28, Piotr M Czerski29, Nina Dalkner22, Alexandre Dayer17, Maria Del Zompo30, J Raymond DePaulo31, Bruno Étain20, Stephane Jamain32, Peter Falkai6, Andreas J Forstner8,27,33, Louise Frisen18,19, Mark A Frye24, Janice M Fullerton34,35, Sébastien Gard36, Julie S Garnham37, Fernando S Goes31, Maria Grigoroiu-Serbanescu38, Paul Grof39, Ryota Hashimoto40,41, Joanna Hauser29, Stefan Herms8,27, Per Hoffmann8,27, Andrea Hofmann8, Esther Jiménez21, Jean-Pierre Kahn42, Layla Kassem4, Po-Hsiu Kuo43, Tadafumi Kato44, John R Kelsoe12, Sarah Kittel-Schneider45, Sebastian Kliwicki46, Barbara König47, Ichiro Kusumi48, Gonzalo Laje4, Mikael Landén49,50, Catharina Lavebratt18,19, Marion Leboyer51, Susan G Leckband52, Alfonso Tortorella53, Mirko Manchia54,55, Lina Martinsson56, Michael J McCarthy12,57, Susan L McElroy58, Francesc Colom59,60, Marina Mitjans16,60,61, Francis M Mondimore31, Palmiero Monteleone62,63, Caroline M Nievergelt12, Markus M Nöthen8, Tomas Novák64, Claire O'Donovan37, Norio Ozaki65, Urban Ösby66, Andrea Pfennig67, James B Potash31, Andreas Reif45, Eva Reininghaus22, Guy A Rouleau68, Janusz K Rybakowski46, Martin Schalling18,19, Peter R Schofield34,35, Barbara W Schweizer31, Giovanni Severino30, Paul D Shilling12, Katzutaka Shimoda69, Christian Simhandl70, Claire M Slaney37, Alessio Squassina30, Thomas Stamm13, Pavla Stopkova64, Mario Maj63, Gustavo Turecki28, Eduard Vieta21, Julia Veeh45, Stephanie H Witt71, Adam Wright72, Peter P Zandi73, Philip B Mitchell72, Michael Bauer67, Martin Alda37,64, Marcella Rietschel71, Francis J McMahon4, Thomas G Schulze4,5,7,31,71, Bernhard T Baune74,75,76.
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.Entities:
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Year: 2020 PMID： 32203155 DOI： 10.1038/s41380-020-0689-5
Source DB: PubMed Journal: Mol Psychiatry ISSN： 1359-4184 Impact factor: 13.437