Dataset Information

Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.

ABSTRACT: Importance:Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ). Objectives:To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association. Design, Setting, and Participants:A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36?989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017. Main Outcomes and Measures:Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained. Results:Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P?

SUBMITTER: International Consortium on Lithium Genetics (ConLi+Gen)

PROVIDER: S-EPMC5833535 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.

Amare Azmeraw T AT Schubert Klaus Oliver KO Hou Liping L Clark Scott R SR Papiol Sergi S Heilbronner Urs U Degenhardt Franziska F Tekola-Ayele Fasil F Hsu Yi-Hsiang YH Shekhtman Tatyana T Adli Mazda M Akula Nirmala N Akiyama Kazufumi K Ardau Raffaella R Arias Bárbara B Aubry Jean-Michel JM Backlund Lena L Bhattacharjee Abesh Kumar AK Bellivier Frank F Benabarre Antonio A Bengesser Susanne S Biernacka Joanna M JM Birner Armin A Brichant-Petitjean Clara C Cervantes Pablo P Chen Hsi-Chung HC Chillotti Caterina C Cichon Sven S Cruceanu Cristiana C Czerski Piotr M PM Dalkner Nina N Dayer Alexandre A Del Zompo Maria M DePaulo J Raymond JR Étain Bruno B Falkai Peter P Forstner Andreas J AJ Frisen Louise L Frye Mark A MA Fullerton Janice M JM Gard Sébastien S Garnham Julie S JS Goes Fernando S FS Grigoroiu-Serbanescu Maria M Grof Paul P Hashimoto Ryota R Hauser Joanna J Herms Stefan S Hoffmann Per P Hofmann Andrea A Jamain Stephane S Jiménez Esther E Kahn Jean-Pierre JP Kassem Layla L Kuo Po-Hsiu PH Kato Tadafumi T Kelsoe John J Kittel-Schneider Sarah S Kliwicki Sebastian S König Barbara B Kusumi Ichiro I Laje Gonzalo G Landén Mikael M Lavebratt Catharina C Leboyer Marion M Leckband Susan G SG Tortorella Alfonso A Manchia Mirko M Martinsson Lina L McCarthy Michael J MJ McElroy Susan S Colom Francesc F Mitjans Marina M Mondimore Francis M FM Monteleone Palmiero P Nievergelt Caroline M CM Nöthen Markus M MM Novák Tomas T O'Donovan Claire C Ozaki Norio N Ösby Urban U Pfennig Andrea A Potash James B JB Reif Andreas A Reininghaus Eva E Rouleau Guy A GA Rybakowski Janusz K JK Schalling Martin M Schofield Peter R PR Schweizer Barbara W BW Severino Giovanni G Shilling Paul D PD Shimoda Katzutaka K Simhandl Christian C Slaney Claire M CM Squassina Alessio A Stamm Thomas T Stopkova Pavla P Maj Mario M Turecki Gustavo G Vieta Eduard E Volkert Julia J Witt Stephanie S Wright Adam A Zandi Peter P PP Mitchell Philip B PB Bauer Michael M Alda Martin M Rietschel Marcella M McMahon Francis J FJ Schulze Thomas G TG Baune Bernhard T BT

JAMA psychiatry 20180101 1

<h4>Importance</h4>Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).<h4>Objectives</h4>To test whether a polygenic score for SCZ is associated with treatment response t ...[more]

PMID: 29121268

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Project description:Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<��.

Dataset Information

Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.

Publications

Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.

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