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Article Dans Une Revue Molecular Psychiatry Année : 2021

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Azmeraw Amare (1, 2) , Klaus Oliver Schubert (1, 3) , Liping Hou (4) , Scott Clark (1) , Sergi Papiol (5) , Micah Cearns (1) , Urs Heilbronner (5, 6) , Franziska Degenhardt (7) , Fasil Tekola-Ayele (4, 8) , Yi-Hsiang Hsu (9, 10) , Tatyana Shekhtman (11) , Mazda Adli (12) , Nirmala Akula (4) , Kazufumi Akiyama (13) , Raffaella Ardau (14) , Bárbara Arias (15, 16) , Jean-Michel Aubry (17) , Lena Backlund (18, 19) , Abesh Kumar Bhattacharjee (11) , Frank Bellivier (20) , Antonio Benabarre (21, 16) , Susanne Bengesser (22) , Joanna Biernacka (23) , Armin Birner (22) , Clara Brichant-Petitjean (20) , Pablo Cervantes (24) , Hsi-Chung Chen (25) , Caterina Chillotti (14) , Sven Cichon (7, 26) , Cristiana Cruceanu (24) , Piotr Czerski (27) , Nina Dalkner (22) , Alexandre Dayer (17) , Maria del Zompo (14) , J. Raymond Depaulo (28) , Bruno Étain (20) , Stephane Jamain (29, 30, 31) , Peter Falkai (5) , Andreas Forstner (7, 26, 32) , Louise Frisen (18, 19) , Mark Frye (23) , Janice Fullerton (33, 34) , Sébastien Gard (35) , Julie Garnham (36) , Fernando Goes (28) , Maria Grigoroiu-Serbanescu (37) , Paul Grof (38) , Ryota Hashimoto (39, 40) , Joanna Hauser (27) , Stefan Herms (7, 26) , Per Hoffmann (7, 26) , Andrea Hofmann (7) , Esther Jiménez (21, 41) , Jean-Pierre Kahn (42, 43) , Layla Kassem (4, 44) , Po-Hsiu Kuo (25) , Tadafumi Kato (45) , John Kelsoe (11) , Sarah Kittel-Schneider (46) , Sebastian Kliwicki (27) , Barbara König (47) , Ichiro Kusumi (48) , Gonzalo Laje (4, 44) , Mikael Landén (49, 18) , Catharina Lavebratt (18, 19) , Marion Leboyer (29, 30, 31) , Susan Leckband (50) , Alfonso Tortorella (51) , Mirko Manchia (14, 36) , Lina Martinsson (18) , Michael Mccarthy (11, 50) , Susan Mcelroy (52) , Francesc Colom (53, 16) , Marina Mitjans (16, 54) , Francis Mondimore (28) , Palmiero Monteleone (55, 56) , Caroline Nievergelt (11) , Markus Nöthen (7) , Tomas Novák (57) , Claire O’donovan (36) , Norio Ozaki (58) , Urban Ösby (19) , Andrea Pfennig (59) , James Potash (28) , Andreas Reif (46) , Eva Reininghaus (60) , Guy Rouleau (61) , Janusz Rybakowski (27) , Martin Schalling (18, 19) , Peter Schofield (33, 34) , Barbara Schweizer (28) , Giovanni Severino (14) , Paul Shilling (11) , Katzutaka Shimoda (13) , Christian Simhandl (62) , Claire Slaney (36) , Alessio Squassina (14) , Thomas Stamm (12) , Pavla Stopkova (57) , Mario Maj (14) , Gustavo Turecki (63) , Eduard Vieta (21, 16) , Julia Veeh (46) , Stephanie Witt (64) , Adam Wright (34, 65) , Peter Zandi (66) , Philip Mitchell (34, 65) , Michael Bauer (59) , Martin Alda (36, 57) , Marcella Rietschel (64) , Francis Mcmahon (4, 44) , Thomas Schulze (64, 4, 44, 6, 28) , Bernhard Baune (67, 68, 69)
1 University of Adelaide
2 SAHMRI - South Australian Health and Medical Research Institute [ Adelaide]
3 Mental Health Services [Adelaide, SA, Australia]
4 NIMH - National Institute of Mental Health
5 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
6 Georg-August-University = Georg-August-Universität Göttingen
7 Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn
8 NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
9 HMS - Harvard Medical School [Boston]
10 Harvard School of Public Health
11 UC San Diego - University of California [San Diego]
12 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
13 Dokkyo Medical University
14 UniCa - Università degli Studi di Cagliari = University of Cagliari
15 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
16 CIBERSAM - Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain]
17 HUG - Geneva University Hospital
18 Karolinska Institutet [Stockholm]
19 Karolinska University Hospital [Stockholm]
20 OPTeN (UMR_S 1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
21 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
22 Karl-Franzens-Universität Graz
23 Mayo Clinic [Rochester]
24 MUHC - McGill University Health Center [Montreal]
25 NTU - National Taiwan University [Taiwan]
26 University Hospital Basel [Basel]
27 PUMS - Poznan University of Medical Sciences [Poland]
28 JHU - Johns Hopkins University
29 IMRB - Institut Mondor de Recherche Biomédicale
30 Fondation FondaMental [Créteil]
31 U955 Inserm - UPEC - IMRB - "Neuropsychiatrie translationnelle" [Créteil]
32 Unibas - Université de Bâle = University of Basel = Basel Universität
33 NRA - Neuroscience Research Australia [Sydney, NSW, Australia]
34 UNSW - University of New South Wales [Sydney]
35 Psychiatrie de l'enfant et de l'adolescent [CH C. Perrens, Bordeaux]
36 Dalhousie University [Halifax]
37 ERA-LEARN - Prof. Dr. Alexandru Obregia Psychiatry Hospital
38 MDCO - Mood Disorders Center of Ottawa
39 Osaka University [Osaka]
40 Graduate School of Medicine [Osaka]
41 CIBER-SAM - Centro de Investigación Biomédica en Red Salud Mental [Madrid]
42 Psychiatrie et Psychologie Clinique de Liaison [CHRU Nancy]
43 CPN - Centre Psychothérapique de Nancy [Laxou]
44 NIH - National Institutes of Health [Bethesda, MD, USA]
45 RIKEN - Environmental Molecular Biology Laboratory
46 Goethe-University Frankfurt am Main
47 LK Neunkirchen - Landesklinikum Neunkirchen
48 Hokkaido University Graduate School of Medicine [Sapporo, Japan]
49 Sahlgrenska Academy at University of Gothenburg [Göteborg]
50 Research Service VA San Diego Healthcare System
51 UNIPG - Università degli Studi di Perugia = University of Perugia
52 UC - University of Cincinnati
53 IMIM-Hospital del Mar
54 MPI - Max Planck Institute of Experimental Medicine [Göttingen]
55 UNISA - Università degli Studi di Salerno = University of Salerno
56 University of the Study of Campania Luigi Vanvitelli
57 NIMH - National Institute of Mental Health [Klecany, Czech Republic]
58 Nagoya University Graduate School of Medicine [Japon]
59 TU Dresden - Technische Universität Dresden = Dresden University of Technology
60 Medical University Graz
61 Montreal Neurological Institute and Hospital
62 SFU - Sigmund Freud University
63 Douglas Mental Health University Institute [Montréal]
64 University of Heidelberg, Medical Faculty
65 Black Dog Institute [Sydney, Australia]
66 Johns Hopkins Bloomberg School of Public Health [Baltimore]
67 WWU - Westfälische Wilhelms-Universität Münster = University of Münster
68 Melbourne Medical School [Melbourne]
69 The Florey Institute of Neuroscience and Mental Health [Parkville, VIC, Australie]
Liping Hou
Scott Clark
Joanna Biernacka
Mark Frye
Julie Garnham
John Kelsoe
Andreas Reif
Paul Shilling
Katzutaka Shimoda

Résumé

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
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Dates et versions

inserm-03130374 , version 1 (03-02-2021)

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Azmeraw Amare, Klaus Oliver Schubert, Liping Hou, Scott Clark, Sergi Papiol, et al.. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder. Molecular Psychiatry, 2021, Online ahead of print. ⟨10.1038/s41380-020-0689-5⟩. ⟨inserm-03130374⟩
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