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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 <jats:italic>HLA<\/jats:italic> region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the <jats:italic>HLA-DRB1*11:01<\/jats:italic> classical allele, associated with a better response to Li (<jats:italic>p<\/jats:italic>\u2009&lt;\u20091\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>; FDR\u2009&lt;\u20090.09 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.<\/jats:p>","DOI":"10.1038\/s41598-021-97140-7","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T10:02:46Z","timestamp":1631095366000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders"],"prefix":"10.1038","volume":"11","author":[{"given":"Sigrid","family":"Le 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MAd has received a grant from Servier, speaker\u2019s fees from Servier, Lundbeck, Aristo, Parexel, Gilead, ViiV, Deutsche Bank, MSD, and MyTomorrows, plus a non-fi nancial support from Lundbeck. KA has received speaker\u2019s fees from Taisho Toyama Pharmaceutical. MAl is funded by a grant of the Canadian Institutes of Health Research. MB has received speaker\u2019s fees from AstraZeneca, Pfi zer, Lilly, Lundbeck, GlaxoSmithKline, Servier, and Ferrer Internacional. B\u00c9 received non-financial support from Labex Biopsy and Fondation Fondamental. RH received grants and speaker honoraria from Dainippon Sumitomo Pharma and Novartis plus speaker honoraria from Eli Lilly Japan, GlaxoSmithKline, Hisamitsu Pharmaceutical, Janssen Pharmaceutical, Nippon Zoki Pharmaceutical, Otsuka Pharmaceutical, Astellas Pharma, Pfi zer, and the Yoshitomiyakuhin Corporation. TK received a grant from Takeda Pharmaceutical and fees from Kyowa Hakko Kirin, Eli Lilly Japan, Otsuka Pharmaceutical, GlaxoSmithKline, Taisho Toyama Pharmaceutical, Dainippon Sumitomo Pharma, Meiji Seika Pharma, Pfi zer Japan, Mochida Pharmaceutical, Shionogi & Co, Janssen Pharmaceutical, Yoshitomiyakuhin Corporation, Agilent Technologies, Astellas Pharma, and Wako Pure Chemical Industries. IK received grants and fees from Dainippon Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Novartis, Otsuka, Ono Pharmaceutical, Pfi zer, Tanabe Mitsubishi Pharma, Takeda Pharmaceutical, Shionogi, and Yoshitomi Pharmaceutical; he received grants from AbbVie GK, Asahi Kasei Pharma, Boehringer Ingelheim, Chugai Pharmaceutical, and Daiichi Sankyo and fees from Astellas Pharma and Janssen Pharmaceutical. MJM served as unpaid consultant for Pathway Genomic (San Diego, USA). SLM received a grant and fees from Naurex and Shire, further grants from Alkermes, Cephalon, Forest, Marriott Foundation, Orexigen Therapeutics, and Takeda Pharmaceutical, he further has served on the advisory boards for Bracket, Hoff mann-La Roche, MedAvante, Sunovion and received fees from Novo Nordisk. PRS received a grant from NHMRC. TGS received a grant and fees from Roche Pharmaceuticals. TSt received personal fees from Servier, Lundbeck, and Bristol-Myers Squibb. EV has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH Research, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis, and Takeda. FC In the last two years he has served as a speaker or in the advisory board of the following companies: Abott, Sandoz and Sanofi and he receives unrestricted research support from Telef\u00f3nica Alpha. JRDP was an unpaid consultant for Assurex Health on behalf of the National Network of Depression Centers and he owns stock in CVS. All above listed interests are outside of the submitted work. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17823"}}