Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder-Reference-Cited by-同舟云学术

Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder

Published:2023-02-14 Issue: Volume: Page:
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Amare Azmeraw¹^ORCID,Thalamuthu Anbupalam²,Schubert Klaus Oliver³^ORCID,Fullerton Janice⁴^ORCID,Ahmed Muktar,Hartmann Simon,Papiol Sergi⁵^ORCID,Heilbronner Urs⁶^ORCID,Degenhardt Franziska⁷,Tekola-Ayele Fasil,Hou Liping⁸,Hsu Yi-Hsiang,Shekhtman Tatyana⁹,Adli Mazda¹⁰,Akula Nirmala,Akiyama Kazufumi¹¹,Ardau Raffaella¹²,Arias Bárbara¹³,Aubry Jean-Michel¹⁴,Backlund Lena,Bhattacharjee Abesh Kumar⁹,Bellivier Frank¹⁵,Benabarre Antoni¹⁶,Bengesser Susanne¹⁷,Biernacka Joanna¹⁸^ORCID,Birner Armin¹⁷,Marie-Claire Cynthia¹⁹^ORCID,Cervantes Pablo²⁰,Chen Hsi-Chung²¹^ORCID,Chillotti Caterina,Cichon Sven²²^ORCID,Cruceanu Cristiana²³^ORCID,Czerski Piotr²⁴^ORCID,Dalkner Nina¹⁷,Zompo Maria Del²⁵^ORCID,DePaulo J. Raymond²⁶,Etain Bruno²⁷^ORCID,Jamain Stéphane²⁸^ORCID,Falkai Peter⁵,Forstner Andreas J.²⁹^ORCID,Frisén Louise³⁰,Frye Mark¹⁸^ORCID,Gard Sébastien³¹,Garnham Julie^ORCID,Goes Fernando³²^ORCID,Grigoroiu-Serbanescu Maria³³^ORCID,Fallgatter Andreas³⁴,Stegmaier Sophia³⁴,Ethofer Thomas³⁵,Biere Silvia³⁵,Petrova Kristiyana³⁵,Schuster Ceylan³⁵,Adorjan Kristina,Budde Monika³⁶,Heilbronner Maria³⁵,Kalman Janos³⁷^ORCID,Kohshour Mojtaba Oraki³⁷,Reich-Erkelenz Daniela³⁸,Schaupp Sabrina³⁵,Schulte Eva⁶^ORCID,Senner Fanny³⁸,Vogl Thomas³⁵,Anghelescu Ion-George,Arolt Volker,Dannlowski Udo,Dietrich Detlef E.,Figge Christian,Jäger Markus,Lang Fabian,Juckel Georg³⁹,Spitzer Carsten,Reimer Jens,Schmauß Max,Schmitt Andrea⁴⁰,Konrad Carsten,von Hagen Martin,Wiltfang Jens⁴¹^ORCID,Zimmermann Jörg,Andlauer Till⁴²^ORCID,Fischer Andre⁴³,Bermpohl Felix⁴⁴,Kraft Vivien,Matura Silke⁴⁵,Gryaznova Anna,Falkenberg Irina,Yildiz Cüneyt,Kircher Tilo,Schmidt Julia,Koch Marius,Gade Katrin,Trost Sarah,Haußleiter Ida,Lambert Martin,Rohenkohl Anja C.,Kraft Vivien⁴⁶^ORCID,Grof Paul⁴⁷,Hashimoto Ryota,Hauser Joanna^ORCID,Herms Stefan,Hoffmann Per⁴⁸,Jiménez Esther,Kahn Jean-Pierre,Kassem Layla,kuo Po-Hsiu⁴⁹^ORCID,Kato Tadafumi,Kelsoe John,Kittel-Schneider Sarah⁵⁰^ORCID,Ferensztajn-Rochowiak Ewa,König Barbara⁵¹,Kusumi Ichiro⁵²^ORCID,Laje Gonzalo,Landén Mikael⁵³^ORCID,Lavebratt Catharina⁵⁴^ORCID,Leboyer Marion^ORCID,Leckband Susan G.⁵⁵,Tortorella Alfonso⁵⁶^ORCID,Manchia Mirko,Martinsson Lina,McCarthy Michael⁵⁵^ORCID,McElroy Susan L.⁵⁷,Colom Francesc⁵⁸,Mitjans Marina⁵⁹,Mondimore Francis²⁶,Monteleone Palmiero⁶⁰,Nievergelt Caroline,Nöthen Markus⁶¹^ORCID,Novak Tomas^ORCID,O'Donovan Claire⁶²,Ozaki Norio⁶⁰,Pfennig Andrea⁶³,Pisanu Claudia²⁵^ORCID,Potash James,Reif Andreas⁶⁴^ORCID,Reininghaus Eva^ORCID,Rouleau Guy⁴⁷^ORCID,Rybakowski Janusz K.²⁴,Schalling Martin⁵⁴^ORCID,Schofield Peter⁴^ORCID,Schweizer Barbara W.²⁶,Severino Giovanni²⁵^ORCID,Shilling Paul D⁶⁰,Shimoda Kazutaka^ORCID,Simhandl Christian,Slaney Claire,Squassina Alessio⁶⁵^ORCID,Stamm Thomas¹⁰,Stopkova Pavla⁸^ORCID,Maj Mario⁶⁶,Turecki Gustavo⁴⁷^ORCID,Vieta Eduard¹⁶^ORCID,Veeh Julia⁶⁷,Witt Stephanie⁶⁸^ORCID,Wright Adam²,Zandi Peter⁶⁹^ORCID,Mitchell Philip,Bauer Michael,Alda Martin⁶²^ORCID,Rietschel Marcella⁷⁰^ORCID,McMahon Francis⁷¹^ORCID,Schulze Thomas G.⁷²,Millischer Vincent¹⁸^ORCID,Clark Scott³^ORCID,Baune Bernhard⁷³

Affiliation:

1. University of Adelaide, AUSTRALIA

2. University of New South Wales

3. University of Adelaide

4. Neuroscience Research Australia

5. University Hospital LMU

6. University Hospital, LMU Munich

7. University of Bonn

8. National Institute of Mental Health

9. University of California San Diego

10. Charité - Universitätsmedizin Berlin, Campus Charité Mitte

11. Dokkyo Medical University School of Medicine

12. Hospital University Agency of Cagliari

13. Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona, CIBERSAM

14. Geneva University Hospitals

15. Pôle de Psychiatrie, AP-HP, Groupe Hospitalier Lariboisière-F. Widal

16. Hospital Clinic of Barcelona

17. Medical University of Graz

18. Mayo Clinic

19. INSERM UMR-S 1144

20. McGill University Health Centre

21. National Taiwan University Hospital

22. Research Center Juelich

23. Max Plank Institute for Psychiatry

24. Poznan University of Medical Sciences

25. University of Cagliari

26. Johns Hopkins University

27. Inserm U955, Psychiatry Genetics

28. Univ Paris Est Creteil, INSERM, IMRB

29. University of Bonn, School of Medicine & University Hospital Bonn

30. Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital

31. Hôpital Charles Perrens

32. fgoes1@jhmi.edu

33. Alexandru Obregia Clinical Psychiatric Hospital

34. University of Tuebingen

35. University Hospital Tübingen

36. Ludwig Maximilian University of Munich

37. Ludwig Maximillians Universitat Muenchen

38. Klinikum der Universität München

39. Ruhr University Bochum

40. Ludwig-Maximilians-University (LMU) Munich

41. Universitätsmedizin Göttingen

42. Technical University of Munich, Klinikum rechts der Isar

43. University of Goettingen, Germany

44. Berlin School of Mind & Brain

45. Goethe University Frankfurt/M.

46. University Medical Center Hamburg-Eppendorf

47. McGill University

48. Institute of Human Genetics

49. College of Public Health, National Taiwan University, Taipei, Taiwan

50. University Hospital of Würzburg

51. Landesklinikum Neunkirchen

52. Hokkaido University Graduate School of Medicine

53. Gothenburg University

54. Karolinska Institutet

55. VA San Diego Healthcare System

56. University of Naples SUN, University of Perugia

57. Lindner Center of Hope / University of Cincinnati

58. Institut Hospital del Mar d'Investigacions Mèdiques

59. Max Planck Institute of Experimental Medicine, Göttingen, Germany

60. University of Salerno

61. School of Medicine & University Hospital Bonn

62. Dalhousie University

63. University Hospital Carl Gustav Carus, TU Dresden

64. University Hospital Frankfurt, Germany

65. Universita degli Studi Di Cagliari

66. University of Campania "Luigi Vanvitelli", Naples

67. University Hospital Frankfurt

68. University Medical Centre Mannheim

69. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine

70. University of Mannheim

71. National Institute of Mental Health Intramural Research Program; National Institutes of Health

72. Ludwig-Maximilians-University Munich

73. The University of Munster

Abstract

Abstract Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response — defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<��

Publisher

Research Square Platform LLC

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