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

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dc.contributor.authorLe Clerc, S.
dc.contributor.authorLombardi, L.
dc.contributor.authorBaune, B.T.
dc.contributor.authorAmare, A.T.
dc.contributor.authorSchubert, K.O.
dc.contributor.authorHou, L.
dc.contributor.authorClark, S.R.
dc.contributor.authorPapiol, S.
dc.contributor.authorCearns, M.
dc.contributor.authorHeilbronner, U.
dc.contributor.authorDegenhardt, F.
dc.contributor.authorTekola-Ayele, F.
dc.contributor.authorHsu, Y.-H.
dc.contributor.authorShekhtman, T.
dc.contributor.authorAdli, M.
dc.contributor.authorAkula, N.
dc.contributor.authorAkiyama, K.
dc.contributor.authorArdau, R.
dc.contributor.authorArias, B.
dc.contributor.authorAubry, J.-M.
dc.contributor.authoret al.
dc.date.issued2021
dc.description.abstractBipolar afective 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 stratifcation are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identifed 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 infammatory/autoimmune processes, our fndings strongly suggest that HLA-mediated low infammatory background may contribute to the efcient response to Li in BD patients, while an infammatory status overriding Li anti-infammatory properties would favor a weak response.
dc.description.statementofresponsibilitySigrid Le Clerc ... Azmeraw T. Amare ... Bernhard T. Baune ... Scott R. Clark ... Klaus O. Schubert ... et al.
dc.identifier.citationScientific Reports, 2021; 11(1):17823-1-17823-12
dc.identifier.doi10.1038/s41598-021-97140-7
dc.identifier.issn2045-2322
dc.identifier.issn2045-2322
dc.identifier.orcidBaune, B.T. [0000-0001-6548-426X]
dc.identifier.orcidAmare, A.T. [0000-0002-7940-0335]
dc.identifier.orcidSchubert, K.O. [0000-0003-1690-0209]
dc.identifier.orcidClark, S.R. [0000-0003-1640-5611]
dc.identifier.orcidCearns, M. [0000-0002-3353-8566]
dc.identifier.urihttps://hdl.handle.net/2440/133804
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1037196
dc.rights© 2021, The Author(s) Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1038/s41598-021-97140-7
dc.subjectHumans
dc.subjectGenetic Predisposition to Disease
dc.subjectLithium
dc.subjectTreatment Outcome
dc.subjectBipolar Disorder
dc.subjectPharmacogenetics
dc.subjectGene Frequency
dc.subjectGenotype
dc.subjectHaplotypes
dc.subjectAlleles
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGenetic Variation
dc.subjectHLA-DQ beta-Chains
dc.subjectHLA-DRB1 Chains
dc.subject.meshHumans
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshLithium
dc.subject.meshTreatment Outcome
dc.subject.meshBipolar Disorder
dc.subject.meshPharmacogenetics
dc.subject.meshGene Frequency
dc.subject.meshGenotype
dc.subject.meshHaplotypes
dc.subject.meshAlleles
dc.subject.meshAdult
dc.subject.meshMiddle Aged
dc.subject.meshFemale
dc.subject.meshMale
dc.subject.meshGenetic Variation
dc.subject.meshHLA-DQ beta-Chains
dc.subject.meshHLA-DRB1 Chains
dc.titleHLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
dc.typeJournal article
pubs.publication-statusPublished

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