TY  - JOUR
A1  - Le Clerc, Sigrid
A1  - Lombardi, Laura
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
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  - Baune, Bernhard T.
A1  - Del Zompo, Maria
A1  - DePaulo, J. Raymond
A1  - Étain, Bruno
A1  - Jamain, Stephane
A1  - Falkai, Peter
A1  - Forstner, Andreas Josef
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  - 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  - Ferensztajn-Rochowiak, Ewa
A1  - König, Barbara
A1  - Kusumi, Ichiro
A1  - Laje, Gonzalo
A1  - Landén, Mikael
A1  - Lavebratt, Catharina
A1  - Leckband, Susan G.
A1  - Tortorella, Alfonso
A1  - Manchia, Mirko
A1  - Martinsson, Lina
A1  - McCarthy, Michael J.
A1  - McElroy, Susan
A1  - Colom, Francesc
A1  - Millischer, Vincent
A1  - Mitjans, Marina
A1  - Mondimore, Francis Mark
A1  - Monteleone, Palmiero
A1  - Nievergelt, Caroline M.
A1  - Nöthen, Markus Maria
A1  - Novák, Tomas
A1  - O'Donovan, Claire
A1  - Ozaki, Norio
A1  - Ösby, Urban
A1  - Pfennig, Andrea
A1  - Potash, James B.
A1  - Reif, Andreas
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  - Pisanu, Claudia
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 Gerd
A1  - Spadoni, Jean-Louis
A1  - Boukouaci, Wahid
A1  - Richard, Jean-Romain
A1  - Le Corvoisier, Philippe
A1  - Barrau, Caroline
A1  - Zagury, Jean-François
A1  - Leboyer, Marion
A1  - Tamouza, Ryad
T1  - HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
T2  - Scientific reports
N2  - 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.
KW  - Genetics
KW  - Immunogenetics
KW  - Immunology
KW  - Psychiatric disorders
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63251
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-632514
SN  - 2045-2322
N1  - This manuscript was written under the framework of Agence Nationale de la Recherche (I-GIVE ANR-13-SAMA-0004-01), INSERM (Institut National de la Santé et de la Recherche Médicale) and Fondation FondaMental. Laura Lombardi benefits from a fellowship n° FDM202006011305 from Fondation de la Recherche Médicale (FRM). Sven Cichon. and Andreas J Forstner received support from the Swiss National Science Foundation / German Research Foundation (SNSF 310030L_182731/1). This work was in part funded by the Deutsche Forschungsgemeinschaft (DFG; grant no RI 908/7-1; grant FOR2107, RI 908/11-1 to Marcella Rietschel, Michael Bauer, and Thomas G Schulze, NO 246/10-1 to MMN) and the Intramural Research Program of the National Institute of Mental Health (ZIA-MH00284311; NCT00001174). The genotyping was in part funded by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med. This work was supported by the NIH grants P50CA89392 from the National Cancer Institute and 5K02DA021237 from the National Institute of Drug Abuse. The Canadian part of the study was supported by a grant #64410 from the Canadian Institutes of Health Research to MAl. Collection and phenotyping of the Australian UNSW sample was funded by an Australian NHMRC Program Grant (No. 1037196).The collection of the Barcelona sample was supported by the Centro de Investigación en Red de Salud Mental (CIBERSAM) IDIBAPS (grant numbers PI080247, PI1200906, PI12/00018), and Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2014SGR1636 and 2014SGR398). Genotyping for part of the Swedish sample was funded by the Stanley Center for Psychiatric Research at the Broad Institute. The Swedish Research Council, the Stockholm County Council, Karolinska Institutet, and the Söderström-Königska Foundation supported this research through grants awarded to Drs Backlund, Frisen, Lavebratt, and Schalling. The collection of the Geneva sample was supported by grants Synapsy–The Synaptic Basis of Mental Diseases 51NF40-158776 and 32003B-125469 from the Swiss National Foundation. The work by the French group was supported by INSERM (Institut National de la Santé et de la Recherche Médicale), AP-HP (Assistance Publique des Hôpitaux de Paris), the Fondation FondaMental (RTRS Santé Mentale), and the labex Bio-PSY (Investissements d’Avenir program managed by the ANR under reference ANR-11-IDEX- 0004-02). The collection of the Romanian sample was supported by a grant from Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (Dr Grigoroiu-Serbanescu).The collection of the Czech sample was supported by the project Nr. LO1611 with a financial support from the MEYS under the NPU I program and by the Czech Science Foundation, grant Nr. 17-07070S.
VL  - 11
IS  - art. 17823
SP  - 1
EP  - 12
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -