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

Le Clerc, S. (author)
Lombardi, L. (author)
Karolinska Institutet
Baune, B. T. (author)
show more...
Amare, A. T. (author)
Schubert, K. O. (author)
Hou, L. P. (author)
Clark, S. R. (author)
Papiol, S. (author)
Cearns, M. (author)
Heilbronner, U. (author)
Degenhardt, F. (author)
Tekola-Ayele, F. (author)
Hsu, Y. H. (author)
Shekhtman, T. (author)
Adli, M. (author)
Akula, N. (author)
Akiyama, K. (author)
Ardau, R. (author)
Arias, B. (author)
Aubry, J. M. (author)
Backlund, L. (author)
Bhattacharjee, A. K. (author)
Bellivier, F. (author)
Benabarre, A. (author)
Bengesser, S. (author)
Biernacka, J. M. (author)
Birner, A. (author)
Brichant-Petitjean, C. (author)
Cervantes, P. (author)
Chen, H. C. (author)
Chillotti, C. (author)
Karolinska Institutet
Cichon, S. (author)
Cruceanu, C. (author)
Czerski, P. M. (author)
Dalkner, N. (author)
Dayer, A. (author)
Del Zompo, M. (author)
DePaulo, J. R. (author)
Etain, B. (author)
Jamain, S. (author)
Falkai, P. (author)
Forstner, A. J. (author)
Frisen, L. (author)
Frye, M. A. (author)
Fullerton, J. M. (author)
Gard, S. (author)
Garnham, J. S. (author)
Goes, F. S. (author)
Grigoroiu-Serbanescu, M. (author)
Grof, P. (author)
Hashimoto, R. (author)
Hauser, J. (author)
Herms, S. (author)
Hofmann, P. (author)
Jimenez, E. (author)
Kahn, J. P. (author)
Kassem, L. (author)
Kuo, P. H. (author)
Kato, T. (author)
Kelsoe, J. R. (author)
Kittel-Schneider, S. (author)
Ferensztajn-Rochowiak, E. (author)
Konig, B. (author)
Kusumi, I. (author)
Laje, G. (author)
Landén, Mikael, 1966 (author)
Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
Lavebratt, C. (author)
Leckband, S. (author)
Tortorella, A. (author)
Manchia, M. (author)
Karolinska Institutet
Martinsson, L. (author)
McCarthy, M. J. (author)
McElroy, S. L. (author)
Colom, F. (author)
Millischer, V. (author)
Karolinska Institutet
Mitjans, M. (author)
Mondimore, F. M. (author)
Monteleone, P. (author)
Nievergelt, C. M. (author)
Nothen, M. M. (author)
Novak, T. (author)
O'Donovan, C. (author)
Ozaki, N. (author)
Osby, U. (author)
Pfennig, A. (author)
Potash, J. B. (author)
Reif, A. (author)
Reininghaus, E. (author)
Rouleau, G. A. (author)
Rybakowski, J. K. (author)
Schalling, M. (author)
Schofeld, P. R. (author)
Schweizer, B. W. (author)
Severino, G. (author)
Shilling, P. D. (author)
Shimoda, K. (author)
Simhandl, C. (author)
Slaney, C. M. (author)
Pisanu, C. (author)
Squassina, A. (author)
Stamm, T. (author)
Stopkova, P. (author)
Maj, M. (author)
Turecki, G. (author)
Vieta, E. (author)
Veeh, J. (author)
Witt, S. H. (author)
Wright, A. (author)
Zandi, P. P. (author)
Mitchell, P. B. (author)
Bauer, M. (author)
Alda, M. (author)
Rietschel, M. (author)
McMahon, F. J. (author)
Schulze, T. G. (author)
Boukouaci, W. (author)
Richard, J. R. (author)
Le Corvoisier, P. (author)
Barrau, C. (author)
Zagury, J. F. (author)
Leboyer, M. (author)
Tamouza, R. (author)
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 (creator_code:org_t)
2021-09-08
2021
English.
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • 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 x 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Keyword

comparative efficacy
class ii
hla
association
disease
risk
prophylaxis
prediction
mania
Science & Technology - Other Topics

Publication and Content Type

ref (subject category)
art (subject category)

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By the author/editor
Le Clerc, S.
Lombardi, L.
Baune, B. T.
Amare, A. T.
Schubert, K. O.
Hou, L. P.
show more...
Clark, S. R.
Papiol, S.
Cearns, M.
Heilbronner, U.
Degenhardt, F.
Tekola-Ayele, F.
Hsu, Y. H.
Shekhtman, T.
Adli, M.
Akula, N.
Akiyama, K.
Ardau, R.
Arias, B.
Aubry, J. M.
Backlund, L.
Bhattacharjee, A ...
Bellivier, F.
Benabarre, A.
Bengesser, S.
Biernacka, J. M.
Birner, A.
Brichant-Petitje ...
Cervantes, P.
Chen, H. C.
Chillotti, C.
Cichon, S.
Cruceanu, C.
Czerski, P. M.
Dalkner, N.
Dayer, A.
Del Zompo, M.
DePaulo, J. R.
Etain, B.
Jamain, S.
Falkai, P.
Forstner, A. J.
Frisen, L.
Frye, M. A.
Fullerton, J. M.
Gard, S.
Garnham, J. S.
Goes, F. S.
Grigoroiu-Serban ...
Grof, P.
Hashimoto, R.
Hauser, J.
Herms, S.
Hofmann, P.
Jimenez, E.
Kahn, J. P.
Kassem, L.
Kuo, P. H.
Kato, T.
Kelsoe, J. R.
Kittel-Schneider ...
Ferensztajn-Roch ...
Konig, B.
Kusumi, I.
Laje, G.
Landén, Mikael, ...
Lavebratt, C.
Leckband, S.
Tortorella, A.
Manchia, M.
Martinsson, L.
McCarthy, M. J.
McElroy, S. L.
Colom, F.
Millischer, V.
Mitjans, M.
Mondimore, F. M.
Monteleone, P.
Nievergelt, C. M ...
Nothen, M. M.
Novak, T.
O'Donovan, C.
Ozaki, N.
Osby, U.
Pfennig, A.
Potash, J. B.
Reif, A.
Reininghaus, E.
Rouleau, G. A.
Rybakowski, J. K ...
Schalling, M.
Schofeld, P. R.
Schweizer, B. W.
Severino, G.
Shilling, P. D.
Shimoda, K.
Simhandl, C.
Slaney, C. M.
Pisanu, C.
Squassina, A.
Stamm, T.
Stopkova, P.
Maj, M.
Turecki, G.
Vieta, E.
Veeh, J.
Witt, S. H.
Wright, A.
Zandi, P. P.
Mitchell, P. B.
Bauer, M.
Alda, M.
Rietschel, M.
McMahon, F. J.
Schulze, T. G.
Boukouaci, W.
Richard, J. R.
Le Corvoisier, P ...
Barrau, C.
Zagury, J. F.
Leboyer, M.
Tamouza, R.
show less...
About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Neurology
Articles in the publication
Scientific Repor ...
By the university
University of Gothenburg
Karolinska Institutet

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