Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder

Azmeraw Amare; Klaus Oliver Schubert; Liping Hou; Scott Clark; Sergi Papiol; Urs Heilbronner; Franziska Degenhardt; Fasil Tekola-Ayele; Yi-Hsiang Hsu; Tatyana Shekhtman; Mazda Adli; Nirmala Akula; Kazufumi Akiyama; Raffaella Ardau; Bárbara Arias; Jean-Michel Aubry; Lena Backlund; Abesh Kumar Bhattacharjee; Frank Bellivier; Antonio Benabarre; Susanne Bengesser; Joanna Biernacka; Armin Birner; Clara Brichant-Petitjean; Pablo Cervantes; Hsi-Chung Chen; Caterina Chillotti; Sven Cichon; Cristiana Cruceanu; Piotr Czerski; Nina Dalkner; Alexandre Dayer; Maria del Zompo; J Raymond Depaulo; Bruno Étain; Peter Falkai; Andreas Forstner; Louise Frisen; Mark Frye; Janice Fullerton; Sébastien Gard; Julie Garnham; Fernando Goes; Maria Grigoroiu-Serbanescu; Paul Grof; Ryota Hashimoto; Joanna Hauser; Stefan Herms; Per Hoffmann; Andrea Hofmann; Stephane Jamain; Esther Jiménez; Jean-Pierre Kahn; Layla Kassem; Po-Hsiu Kuo; Tadafumi Kato; John Kelsoe; Sarah Kittel-Schneider; Sebastian Kliwicki; Barbara König; Ichiro Kusumi; Gonzalo Laje; Mikael Landén; Catharina Lavebratt; Marion Leboyer; Susan Leckband; Alfonso Tortorella; Mirko Manchia; Lina Martinsson; Michael Mccarthy; Susan Mcelroy; Francesc Colom; Marina Mitjans; Francis Mondimore; Palmiero Monteleone; Caroline Nievergelt; Markus Nöthen; Tomas Novák; Claire O'Donovan; Norio Ozaki; Urban Ösby; Andrea Pfennig; James Potash; Andreas Reif; Eva Reininghaus; Guy Rouleau; Janusz Rybakowski; Martin Schalling; Peter Schofield; Barbara Schweizer; Giovanni Severino; Paul Shilling; Katzutaka Shimoda; Christian Simhandl; Claire Slaney; Alessio Squassina; Thomas Stamm; Pavla Stopkova; Mario Maj; Gustavo Turecki; Eduard Vieta; Julia Volkert; Stephanie Witt; Adam Wright; Peter Zandi; Philip Mitchell; Michael Bauer; Martin Alda; Marcella Rietschel; Francis Mcmahon; Thomas Schulze; Bernhard Baune; J. Raymond Depaulo; Claire O’donovan

doi:10.1001/jamapsychiatry.2017.3433

Journal Articles JAMA Psychiatry Year : 2018

Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder

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Azmeraw Amare

Function : Author

Klaus Oliver Schubert

Function : Author

Liping Hou

Function : Author

Scott Clark

Function : Author

Sergi Papiol

Function : Author

Urs Heilbronner

Function : Author

Franziska Degenhardt

Function : Author

Fasil Tekola-Ayele

Function : Author

Yi-Hsiang Hsu

Function : Author

Tatyana Shekhtman

Function : Author

Mazda Adli

Function : Author

Nirmala Akula

Function : Author

Kazufumi Akiyama

Function : Author

Raffaella Ardau

Function : Author

Bárbara Arias

Function : Author

Jean-Michel Aubry

Function : Author

Lena Backlund

Function : Author

Abesh Kumar Bhattacharjee

Function : Author

Frank Bellivier

Function : Author

Optimisation thérapeutique en Neuropsychopharmacologie

Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Antonio Benabarre

Function : Author

Susanne Bengesser

Function : Author

Joanna Biernacka

Function : Author

Armin Birner

Function : Author

Clara Brichant-Petitjean

Function : Author

Optimisation thérapeutique en Neuropsychopharmacologie

Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Pablo Cervantes

Function : Author

Hsi-Chung Chen

Function : Author

Caterina Chillotti

Function : Author

Sven Cichon

Function : Author

Cristiana Cruceanu

Function : Author

Piotr Czerski

Function : Author

Nina Dalkner

Function : Author

Alexandre Dayer

Function : Author

Maria del Zompo

Function : Author

J Raymond Depaulo

Function : Author

Bruno Étain

Function : Author
PersonId : 757741
IdHAL : bruno-etain
ORCID : 0000-0002-5377-1488
IdRef : 074181106

Optimisation thérapeutique en Neuropsychopharmacologie

Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Peter Falkai

Function : Author

Andreas Forstner

Function : Author

Louise Frisen

Function : Author

Mark Frye

Function : Author

Janice Fullerton

Function : Author

Sébastien Gard

Function : Author

Julie Garnham

Function : Author

Fernando Goes

Function : Author

Maria Grigoroiu-Serbanescu

Function : Author

Paul Grof

Function : Author

Ryota Hashimoto

Function : Author

Joanna Hauser

Function : Author

Stefan Herms

Function : Author

Per Hoffmann

Function : Author

Andrea Hofmann

Function : Author

Stephane Jamain

Function : Author

IMRB - "Neuropsychiatrie translationnelle" [Créteil]

Esther Jiménez

Function : Author

Jean-Pierre Kahn

Function : Author

Centre Psychothérapique de Nancy [Laxou]

Layla Kassem

Function : Author

Po-Hsiu Kuo

Function : Author

Tadafumi Kato

Function : Author

John Kelsoe

Function : Author

Sarah Kittel-Schneider

Function : Author

Sebastian Kliwicki

Function : Author

Barbara König

Function : Author

Ichiro Kusumi

Function : Author

Gonzalo Laje

Function : Author

Mikael Landén

Function : Author

Catharina Lavebratt

Function : Author

Marion Leboyer

Function : Author

IMRB - "Neuropsychiatrie translationnelle" [Créteil]

Pôle de Psychiatrie [Hôpital Henri Mondor]

Susan Leckband

Function : Author

Alfonso Tortorella

Function : Author

Mirko Manchia

Function : Author

Lina Martinsson

Function : Author

Michael Mccarthy

Function : Author

Susan Mcelroy

Function : Author

Francesc Colom

Function : Author

Marina Mitjans

Function : Author

Francis Mondimore

Function : Author

Palmiero Monteleone

Function : Author

Caroline Nievergelt

Function : Author

Markus Nöthen

Function : Author

Tomas Novák

Function : Author

Claire O'Donovan

Function : Author

Norio Ozaki

Function : Author

Urban Ösby

Function : Author

Andrea Pfennig

Function : Author

James Potash

Function : Author

Andreas Reif

Function : Author

Eva Reininghaus

Function : Author

Guy Rouleau

Function : Author

Janusz Rybakowski

Function : Author

Martin Schalling

Function : Author

Peter Schofield

Function : Author

Barbara Schweizer

Function : Author

Giovanni Severino

Function : Author

Paul Shilling

Function : Author

Katzutaka Shimoda

Function : Author

Christian Simhandl

Function : Author

Claire Slaney

Function : Author

Alessio Squassina

Function : Author

Thomas Stamm

Function : Author

Pavla Stopkova

Function : Author

Mario Maj

Function : Author

Gustavo Turecki

Function : Author

Eduard Vieta

Function : Author

Julia Volkert

Function : Author

Stephanie Witt

Function : Author

Adam Wright

Function : Author

Peter Zandi

Function : Author

Philip Mitchell

Function : Author

Michael Bauer

Function : Author

Martin Alda

Function : Author

Marcella Rietschel

Function : Author

Francis Mcmahon

Function : Author

Thomas Schulze

Function : Author

Bernhard Baune

Function : Author

J. Raymond Depaulo

Function : Author

Claire O’donovan

Function : Author

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 < 5 × 10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines. Conclusions and relevance: This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium. Trial registration: ClinicalTrials.gov NCT00001174.

Domains

Psychiatrics and mental health

Bruno Etain : Connect in order to contact the contributor

https://www.hal.inserm.fr/inserm-03854545

Submitted on : Tuesday, November 15, 2022-7:30:45 PM

Last modification on : Wednesday, March 22, 2023-4:18:26 AM

Dates and versions

inserm-03854545 , version 1 (15-11-2022)

Identifiers

HAL Id : inserm-03854545 , version 1
DOI : 10.1001/jamapsychiatry.2017.3433
PUBMED : 29121268
PUBMEDCENTRAL : PMC5833535

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Azmeraw Amare, Klaus Oliver Schubert, Liping Hou, Scott Clark, Sergi Papiol, et al.. Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder. JAMA Psychiatry, 2018, 75 (1), pp.65-74. ⟨10.1001/jamapsychiatry.2017.3433⟩. ⟨inserm-03854545⟩

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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder

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