Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder
Creators: name: Herrera-Rivero, Marisol
name: Gutiérrez-Fragoso, Karina
name: Thalamuthu, Anbupalam
name: Amare, Azmeraw T.
name: Adli, Mazda
name: Akiyama, Kazufumi
name: Akula, Nirmala
name: Ardau, Raffaella
name: Arias, Bárbara
name: Aubry, Jean-Michel
name: Backlund, Lena
name: Bellivier, Frank
name: Benabarre, Antonio
name: Bengesser, Susanne
name: Abesh, Bhattacharjee
name: Biernacka, Joanna
name: Birner, Armin
name: Cearns, Micah
name: Cervantes, Pablo
name: Chen, Hsi-Chung
name: Chillotti, Caterina
name: Cichon, Sven
name: Clark, Scott
name: Colom, Francesc
name: Cruceanu, Cristiana
name: Czerski, Piotr
name: Dalkner, Nina
name: Degenhardt, Franziska
name: Zompo, Maria Del
name: DePaulo, J. Raymond
name: Etain, Bruno
name: Falkai, Peter
name: Ferensztajn-Rochowiak, Ewa
name: Forstner, Andreas J.
name: Frank, Josef
name: Frisen, Louise
name: Frye, Mark
name: Fullerton, Janice
name: Gallo, Carla
name: Gard, Sebastien
name: Garnham, Julie
name: Goes, Fernando
name: Grigoroiu-Serbanescu, Maria
name: Grof, Paul
name: Hashimoto, Ryota
name: Hasler, Roland
name: Hauser, Joanna
name: Heilbronner, Urs
name: Herms, Stefan
name: Hoffmann, Per
name: Hou, Liping
name: Hsu, YiHsiang
name: Jamain, Stéphane
name: Jiménez, Esther
name: Kahn, Jean-Pierre
name: Kassem, Layla
name: Kato, Tadafumi
name: Kelsoe, John
name: Kittel-Schneider, Sarah
name: kuo, Po-Hsiu
name: Kurtz, Joachim
name: Kusumi, Ichiro
name: König, Barbara
name: Laje, Gonzalo
name: Landén, Mikael
name: Lavebratt, Catharina
name: Leboyer, Marion
name: Leckband, Susan
name: Maj, Mario
name: Manchia, Mirko
name: Marie-Claire, Cynthia
name: Martinsson, Lina
name: McCarthy, Michael
name: McElroy, Susan L.
name: Millischer, Vincent
name: Mitjans, Marina
name: Mondimore, Francis
name: Monteleone, Palmiero
name: Nievergelt, Caroline
name: Novak, Tomas
name: Nöthen, Markus
name: odonovan, claire
name: Ozaki, Norio
name: Papiol, Sergi
name: Pfennig, Andrea
name: Pisanu, Claudia
name: Potash, James
name: Reif, Andreas
name: Reininghaus, Eva
name: Richard-Lepouriel, Hélène
name: Roberts, Gloria
name: Rouleau, Guy
name: Rybakowski, Janusz K.
name: Schalling, Martin
name: Schofield, Peter
name: Schubert, Klaus Oliver
name: Schulte, Eva
name: SCHWEIZER, BARBARA
name: Severino, Giovanni
name: Shekhtman, Tatyana
name: Shilling, Paul
name: Shimoda, Kazutaka
name: Simhandl, Christian
name: slaney, claire
name: Squassina, Alessio
name: Stamm, Thomas
name: Stopkova, Pavla
name: Streit, Fabian
name: Ayele, Fasil
name: Tortorella, Alfonso
name: Turecki, Gustavo
name: Veeh, Julia
name: Vieta, Eduard
name: Viswanath, Biju
name: Witt, Stephanie
name: Zandi, Peter
name: Alda, Martin
name: Bauer, Michael
name: McMahon, Francis
name: Mitchell, Philip
name: Rietschel, Marcella
name: Schulze, Thomas
name: Baune, Bernhard
Publisher: name: Forschungzentrum Jülich
Year: 2023

description: doi:10.21203/rs.3.rs-3068352/v1
description: The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi + Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p &lt; 1x10 - 4 values, including HAS3 , CNTNAP5 and NFIB . Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4 , XKR4 , NRXN1 , NRG1/3 and GRK5 . Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.