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Journal Articles Scientific Reports Year : 2021

HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders

Sigrid Le Clerc (1) , Laura Lombardi (2, 3, 4) , Bernhard T Baune (5, 6, 7) , Azmeraw T Amare (8) , Klaus Oliver Schubert (8) , Liping Hou (9) , Scott R Clark (8) , Sergi Papiol (10) , Micah Cearns (8) , Urs Heilbronner (10) , Franziska Degenhardt (11) , 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 (12) , Antonio Benabarre , Susanne Bengesser , Joanna M Biernacka , Armin Birner , Clara Brichant-Petitjean (12) , Pablo Cervantes , Hsi-Chung Chen , Caterina Chillotti , Sven Cichon , Cristiana Cruceanu , Piotr M Czerski , Nina Dalkner , Alexandre Dayer , Maria del Zompo , J. Raymond Raymond Depaulo , Bruno Étain (12) , Stephane Jamain , Peter Falkai , Andreas J Forstner , Louise Frisen , Mark A Frye , Janice M Fullerton , Sébastien Gard , Julie S Garnham , Fernando S Goes , Maria Grigoroiu-Serbanescu , Paul Grof , Ryota Hashimoto , Joanna Hauser , Stefan Herms , Per Hoffmann , Esther Jiménez , Jean-Pierre Kahn , Layla Kassem , Po-Hsiu Kuo , Tadafumi Kato , John R Kelsoe , Sarah Kittel-Schneider , Ewa Ferensztajn-Rochowiak , Barbara König , Ichiro Kusumi , Gonzalo Laje , Mikael Landén , Catharina Lavebratt , Susan G Leckband , Alfonso Tortorella , Mirko Manchia , Lina Martinsson , Michael J Mccarthy , Susan L Mcelroy , Francesc Colom , Vincent Millischer , Marina Mitjans , Francis M Mondimore , Palmiero Monteleone , Caroline M Nievergelt , Markus M Nöthen , Tomas Novák , Claire O’donovan , Norio Ozaki , Urban Ösby , Andrea Pfennig , James B Potash , Andreas Reif , Eva Reininghaus , Guy A Rouleau , Janusz K Rybakowski , Martin Schalling , Peter R Schofield , Barbara W Schweizer , Giovanni Severino , Paul D Shilling , Katzutaka Shimoda , Christian Simhandl , Claire M Slaney , Claudia Pisanu , Alessio Squassina , Thomas Stamm , Pavla Stopkova , Mario Maj , Gustavo Turecki , Eduard Vieta , Julia Veeh , Stephanie H Witt , Adam Wright , Peter P Zandi , Philip B Mitchell , Michael Bauer , Martin Alda , Marcella Rietschel , Francis J Mcmahon , Thomas G Schulze , Jean-Louis Spadoni (1) , Wahid Boukouaci , Jean-Romain Richard , Philippe Le Corvoisier , Caroline Barrau , Jean-François Zagury (1) , Marion Leboyer , Ryad Tamouza (3, 2, 4)
Klaus Oliver Schubert
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
Antonio Benabarre
  • Function : Author
Susanne Bengesser
  • Function : Author
Joanna M Biernacka
  • Function : Author
Armin Birner
  • Function : Author
Pablo Cervantes
  • Function : Author
Hsi-Chung Chen
  • Function : Author
Caterina Chillotti
  • Function : Author
Sven Cichon
  • Function : Author
Cristiana Cruceanu
Piotr M Czerski
  • Function : Author
Nina Dalkner
  • Function : Author
Alexandre Dayer
  • Function : Author
Maria del Zompo
J. Raymond Raymond Depaulo
  • Function : Author
Stephane Jamain
Peter Falkai
  • Function : Author
Andreas J Forstner
  • Function : Author
Louise Frisen
  • Function : Author
Mark A Frye
  • Function : Author
Janice M Fullerton
  • Function : Author
Sébastien Gard
  • Function : Author
Julie S Garnham
  • Function : Author
Fernando S Goes
  • Function : Author
Maria Grigoroiu-Serbanescu
Paul Grof
  • Function : Author
Ryota Hashimoto
  • Function : Author
Joanna Hauser
Stefan Herms
Per Hoffmann
  • Function : Author
Esther Jiménez
  • Function : Author
Jean-Pierre Kahn
  • Function : Author
Layla Kassem
  • Function : Author
Po-Hsiu Kuo
  • Function : Author
Tadafumi Kato
  • Function : Author
John R Kelsoe
  • Function : Author
Sarah Kittel-Schneider
  • Function : Author
Ewa Ferensztajn-Rochowiak
  • Function : Author
Barbara König
  • Function : Author
Ichiro Kusumi
Gonzalo Laje
  • Function : Author
Mikael Landén
Catharina Lavebratt
Susan G Leckband
  • Function : Author
Alfonso Tortorella
  • Function : Author
Mirko Manchia
  • Function : Author
Lina Martinsson
  • Function : Author
Michael J Mccarthy
  • Function : Author
Susan L Mcelroy
  • Function : Author
Francesc Colom
  • Function : Author
Vincent Millischer
  • Function : Author
Marina Mitjans
  • Function : Author
Francis M Mondimore
  • Function : Author
Palmiero Monteleone
  • Function : Author
Caroline M Nievergelt
  • Function : Author
Markus M Nöthen
  • Function : Author
Tomas Novák
Claire O’donovan
  • Function : Author
Norio Ozaki
Urban Ösby
  • Function : Author
Andrea Pfennig
  • Function : Author
James B Potash
  • Function : Author
Andreas Reif
Eva Reininghaus
  • Function : Author
Guy A Rouleau
Janusz K Rybakowski
  • Function : Author
Martin Schalling
  • Function : Author
Peter R Schofield
  • Function : Author
Barbara W Schweizer
  • Function : Author
Giovanni Severino
Paul D Shilling
  • Function : Author
Katzutaka Shimoda
Christian Simhandl
  • Function : Author
Claire M Slaney
  • Function : Author
Claudia Pisanu
Alessio Squassina
Thomas Stamm
  • Function : Author
Pavla Stopkova
  • Function : Author
Mario Maj
  • Function : Author
Gustavo Turecki
Eduard Vieta
  • Function : Author
Julia Veeh
  • Function : Author
Stephanie H Witt
  • Function : Author
Adam Wright
  • Function : Author
Peter P Zandi
  • Function : Author
Philip B Mitchell
  • Function : Author
Michael Bauer
Martin Alda
Marcella Rietschel
Francis J Mcmahon
  • Function : Author
Thomas G Schulze
  • Function : Author
Wahid Boukouaci
  • Function : Author
Jean-Romain Richard
  • Function : Author
Philippe Le Corvoisier
Caroline Barrau
  • Function : Author
Marion Leboyer

Abstract

Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li ( p < 1 × 10 −3 ; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
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hal-03500675 , version 1 (22-12-2021)

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Sigrid Le Clerc, Laura Lombardi, Bernhard T Baune, Azmeraw T Amare, Klaus Oliver Schubert, et al.. HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders. Scientific Reports, 2021, 11 (1), ⟨10.1038/s41598-021-97140-7⟩. ⟨hal-03500675⟩
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