Association of polygenic score for major depression with response to lithium in patients with bipolar disorder - Archive ouverte HAL
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 = Berlin University Medicine
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
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 of Graz = Medizinische Universität 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]
Azmeraw Amare
University of Adelaide
South Australian Health and Medical Research Institute [ Adelaide]
Klaus Oliver Schubert
University of Adelaide
Mental Health Services [Adelaide, SA, Australia]
Liping Hou
National Institute of Mental Health
Scott Clark
University of Adelaide
Sergi Papiol
Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
Micah Cearns
  • Fonction : Auteur
University of Adelaide
Urs Heilbronner
Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
Georg-August-University = Georg-August-Universität Göttingen
Franziska Degenhardt
  • Fonction : Auteur
Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn
Fasil Tekola-Ayele
  • Fonction : Auteur
National Institute of Mental Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Yi-Hsiang Hsu
  • Fonction : Auteur
Harvard Medical School [Boston]
Harvard School of Public Health
Tatyana Shekhtman
  • Fonction : Auteur
University of California [San Diego]
Mazda Adli
  • Fonction : Auteur
Charité - UniversitätsMedizin = Berlin University Medicine
Nirmala Akula
  • Fonction : Auteur
National Institute of Mental Health
Kazufumi Akiyama
  • Fonction : Auteur
Dokkyo Medical University
Raffaella Ardau
  • Fonction : Auteur
Università degli Studi di Cagliari = University of Cagliari
Bárbara Arias
  • Fonction : Auteur
Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain]
Jean-Michel Aubry
  • Fonction : Auteur
Geneva University Hospital
Lena Backlund
  • Fonction : Auteur
Karolinska Institutet [Stockholm]
Karolinska University Hospital [Stockholm]
Abesh Kumar Bhattacharjee
  • Fonction : Auteur
University of California [San Diego]
Frank Bellivier
Optimisation thérapeutique en Neuropsychopharmacologie
Antonio Benabarre
  • Fonction : Auteur
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain]
Susanne Bengesser
  • Fonction : Auteur
Karl-Franzens-Universität Graz
Joanna Biernacka
Mayo Clinic [Rochester]
Armin Birner
  • Fonction : Auteur
Karl-Franzens-Universität Graz
Clara Brichant-Petitjean
  • Fonction : Auteur
Optimisation thérapeutique en Neuropsychopharmacologie
Pablo Cervantes
  • Fonction : Auteur
McGill University Health Center [Montreal]
Hsi-Chung Chen
  • Fonction : Auteur
National Taiwan University [Taiwan]
Caterina Chillotti
  • Fonction : Auteur
Università degli Studi di Cagliari = University of Cagliari
Sven Cichon
  • Fonction : Auteur
Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn
University Hospital Basel [Basel]
Cristiana Cruceanu
McGill University Health Center [Montreal]
Piotr Czerski
Poznan University of Medical Sciences [Poland]
Nina Dalkner
  • Fonction : Auteur
Karl-Franzens-Universität Graz
Alexandre Dayer
  • Fonction : Auteur
Geneva University Hospital
Maria del Zompo
Università degli Studi di Cagliari = University of Cagliari
J. Raymond Depaulo
  • Fonction : Auteur
Johns Hopkins University
Bruno Étain
Optimisation thérapeutique en Neuropsychopharmacologie
CV
Stephane Jamain
Institut Mondor de Recherche Biomédicale
Fondation FondaMental [Créteil]
IMRB - "Neuropsychiatrie translationnelle" [Créteil]
CV
Peter Falkai
  • Fonction : Auteur
Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
Andreas Forstner
Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn
University Hospital Basel [Basel]
Université de Bâle = University of Basel = Basel Universität
Louise Frisen
  • Fonction : Auteur
Karolinska Institutet [Stockholm]
Karolinska University Hospital [Stockholm]
Mark Frye
Mayo Clinic [Rochester]
Janice Fullerton
Neuroscience Research Australia [Sydney, NSW, Australia]
University of New South Wales [Sydney]
Sébastien Gard
  • Fonction : Auteur
Psychiatrie de l'enfant et de l'adolescent [CH C. Perrens, Bordeaux]
Julie Garnham
Dalhousie University [Halifax]
Fernando Goes
  • Fonction : Auteur
Johns Hopkins University
Maria Grigoroiu-Serbanescu
Prof. Dr. Alexandru Obregia Psychiatry Hospital
Paul Grof
  • Fonction : Auteur
Mood Disorders Center of Ottawa
Ryota Hashimoto
  • Fonction : Auteur
Osaka University [Osaka]
Graduate School of Medicine [Osaka]
Joanna Hauser
Poznan University of Medical Sciences [Poland]
Stefan Herms
Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn
University Hospital Basel [Basel]
Per Hoffmann
  • Fonction : Auteur
Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn
University Hospital Basel [Basel]
Andrea Hofmann
  • Fonction : Auteur
Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn
Esther Jiménez
  • Fonction : Auteur
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Centro de Investigación Biomédica en Red Salud Mental [Madrid]
Jean-Pierre Kahn
  • Fonction : Auteur
Psychiatrie et Psychologie Clinique de Liaison [CHRU Nancy]
Centre Psychothérapique de Nancy [Laxou]
Layla Kassem
  • Fonction : Auteur
National Institute of Mental Health
National Institutes of Health [Bethesda, MD, USA]
Po-Hsiu Kuo
  • Fonction : Auteur
National Taiwan University [Taiwan]
Tadafumi Kato
  • Fonction : Auteur
Environmental Molecular Biology Laboratory
John Kelsoe
University of California [San Diego]
Sarah Kittel-Schneider
  • Fonction : Auteur
Goethe University Frankfurt
Sebastian Kliwicki
  • Fonction : Auteur
Poznan University of Medical Sciences [Poland]
Barbara König
  • Fonction : Auteur
Landesklinikum Neunkirchen
Ichiro Kusumi
Hokkaido University Graduate School of Medicine [Sapporo, Japan]
Gonzalo Laje
  • Fonction : Auteur
National Institute of Mental Health
National Institutes of Health [Bethesda, MD, USA]
Mikael Landén
Sahlgrenska Academy at University of Gothenburg [Göteborg]
Karolinska Institutet [Stockholm]
Catharina Lavebratt
Karolinska Institutet [Stockholm]
Karolinska University Hospital [Stockholm]
Marion Leboyer
Institut Mondor de Recherche Biomédicale
Fondation FondaMental [Créteil]
IMRB - "Neuropsychiatrie translationnelle" [Créteil]
Susan Leckband
  • Fonction : Auteur
Research Service VA San Diego Healthcare System
Alfonso Tortorella
  • Fonction : Auteur
Università degli Studi di Perugia = University of Perugia
Mirko Manchia
  • Fonction : Auteur
Università degli Studi di Cagliari = University of Cagliari
Dalhousie University [Halifax]
Lina Martinsson
  • Fonction : Auteur
Karolinska Institutet [Stockholm]
Michael Mccarthy
  • Fonction : Auteur
University of California [San Diego]
Research Service VA San Diego Healthcare System
Susan Mcelroy
  • Fonction : Auteur
University of Cincinnati
Francesc Colom
  • Fonction : Auteur
IMIM-Hospital del Mar
Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain]
Marina Mitjans
  • Fonction : Auteur
Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain]
Max Planck Institute of Experimental Medicine [Göttingen]
Francis Mondimore
  • Fonction : Auteur
Johns Hopkins University
Palmiero Monteleone
  • Fonction : Auteur
Università degli Studi di Salerno = University of Salerno
University of the Study of Campania Luigi Vanvitelli
Caroline Nievergelt
University of California [San Diego]
Markus Nöthen
Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn
Tomas Novák
National Institute of Mental Health [Klecany, Czech Republic]
Claire O’donovan
  • Fonction : Auteur
Dalhousie University [Halifax]
Norio Ozaki
Nagoya University Graduate School of Medicine [Japon]
Urban Ösby
  • Fonction : Auteur
Karolinska University Hospital [Stockholm]
Andrea Pfennig
  • Fonction : Auteur
Technische Universität Dresden = Dresden University of Technology
James Potash
  • Fonction : Auteur
Johns Hopkins University
Andreas Reif
Goethe University Frankfurt
Eva Reininghaus
  • Fonction : Auteur
Medical University of Graz = Medizinische Universität Graz
Guy Rouleau
Montreal Neurological Institute and Hospital
Janusz Rybakowski
  • Fonction : Auteur
Poznan University of Medical Sciences [Poland]
Martin Schalling
  • Fonction : Auteur
Karolinska Institutet [Stockholm]
Karolinska University Hospital [Stockholm]
Peter Schofield
Neuroscience Research Australia [Sydney, NSW, Australia]
University of New South Wales [Sydney]
Barbara Schweizer
  • Fonction : Auteur
Johns Hopkins University
Giovanni Severino
Università degli Studi di Cagliari = University of Cagliari
Paul Shilling
University of California [San Diego]
Katzutaka Shimoda
Dokkyo Medical University
Christian Simhandl
  • Fonction : Auteur
Sigmund Freud University
Claire Slaney
  • Fonction : Auteur
Dalhousie University [Halifax]
Alessio Squassina
Università degli Studi di Cagliari = University of Cagliari
Thomas Stamm
  • Fonction : Auteur
Charité - UniversitätsMedizin = Berlin University Medicine
Pavla Stopkova
  • Fonction : Auteur
National Institute of Mental Health [Klecany, Czech Republic]
Mario Maj
  • Fonction : Auteur
Università degli Studi di Cagliari = University of Cagliari
Gustavo Turecki
Douglas Mental Health University Institute [Montréal]
Eduard Vieta
  • Fonction : Auteur
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain]
Julia Veeh
  • Fonction : Auteur
Goethe University Frankfurt
Stephanie Witt
University of Heidelberg, Medical Faculty
Adam Wright
  • Fonction : Auteur
University of New South Wales [Sydney]
Black Dog Institute [Sydney, Australia]
Peter Zandi
  • Fonction : Auteur
Johns Hopkins Bloomberg School of Public Health [Baltimore]
Philip Mitchell
University of New South Wales [Sydney]
Black Dog Institute [Sydney, Australia]
Michael Bauer
Technische Universität Dresden = Dresden University of Technology
Martin Alda
Dalhousie University [Halifax]
National Institute of Mental Health [Klecany, Czech Republic]
Marcella Rietschel
University of Heidelberg, Medical Faculty
Francis Mcmahon
National Institute of Mental Health
National Institutes of Health [Bethesda, MD, USA]
Thomas Schulze
University of Heidelberg, Medical Faculty
National Institute of Mental Health
National Institutes of Health [Bethesda, MD, USA]
Georg-August-University = Georg-August-Universität Göttingen
Johns Hopkins University
Bernhard Baune
Westfälische Wilhelms-Universität Münster = University of Münster
Melbourne Medical School [Melbourne]
The Florey Institute of Neuroscience and Mental Health [Parkville, VIC, Australie]

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.

Domaines

Psychiatrie et santé mentale Génétique humaine
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https://inserm.hal.science/inserm-03130374

Soumis le : mercredi 3 février 2021-15:15:30

Dernière modification le : mardi 19 novembre 2024-14:04:09

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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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