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Article Dans Une Revue Biological Psychiatry: Cognitive Neuroscience and Neuroimaging Année : 2021

Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Gabriëlla A.M. Blokland (1, 2) , Jakob Grove (3, 4) , Chia-Yen Chen (2, 5) , Chris Cotsapas (6) , Stuart Tobet (2, 7) , Robert Handa (2, 7) , David St Clair (8, 9) , Todd Lencz (10, 11, 12) , Bryan J. Mowry (13, 14) , Sathish Periyasamy (13, 14) , Murray J. Cairns (15, 16) , Paul A. Tooney (16) , Jing Qin Wu (16, 15) , Brian Kelly (16) , George Kirov (17, 18) , Patrick F. Sullivan (19, 20) , Aiden Corvin (21) , Brien P. Riley (22) , Tõnu Esko (5, 23) , Lili Milani (5, 24) , Erik G. Jönsson (20, 25) , Aarno Palotie (2, 23, 5, 26) , Hannelore Ehrenreich (27) , Martin Begemann (27) , Agnes Steixner-Kumar (27) , Pak C. Sham (28, 29) , Nakao Iwata (30) , Daniel R. Weinberger (31, 32) , Pablo V. Gejman (33, 34) , Alan R. Sanders (33, 34) , Joseph D. Buxbaum (35) , Dan Rujescu (36, 37) , Ina Giegling (36, 37) , Bettina Konte (36) , Annette M. Hartmann (36) , Elvira Bramon (38) , Robin M. Murray (39) , Michele T. Pato (40, 41) , Jimmy Lee (42, 43) , Ingrid Melle (25, 44, 45) , Espen Molden (46, 44) , Roel A. Ophoff (47, 48) , Andrew Mcquillin (38) , Nicholas J. Bass (38) , Rolf Adolfsson (49) , Anil K. Malhotra (10, 11, 12) , Nicholas G. Martin (14, 50) , Janice M. Fullerton (51, 52) , Philip B. Mitchell (52) , Peter R. Schofield (51, 52) , Andreas J. Forstner (53, 54) , Franziska Degenhardt (55, 54, 56) , Sabrina Schaupp (57, 37) , Ashley L. Comes (57, 37, 58) , Manolis Kogevinas (59) , José Guzman-Parra (60) , Andreas Reif (61) , Fabian Streit (62, 63) , Lea Sirignano (62, 63) , Sven Cichon (54, 64, 65) , Maria Grigoroiu-Serbanescu (66) , Joanna Hauser (67) , Jolanta Lissowska (68) , Fermin Mayoral (60) , Bertram Müller-Myhsok (69, 70) , Beata Świątkowska (71) , Thomas G. Schulze (72, 32, 37, 62, 63, 73) , Markus M. Nöthen (54, 64) , Marcella Rietschel (62, 63) , John Kelsoe (74) , Marion Leboyer (75, 76, 77) , Stéphane Jamain (77) , Bruno Etain (78, 79, 80) , Frank Bellivier (78, 79, 81, 82) , John B. Vincent (83) , Martin Alda (84, 85) , Claire O’donovan (84) , Pablo Cervantes (86) , Joanna M. Biernacka (87) , Mark Frye (87) , Susan L. Mcelroy (88) , Laura J. Scott (89) , Eli A. Stahl (5, 35) , Mikael Landén (20, 90) , Marian L. Hamshere (17) , Olav B. Smeland (25, 45) , Srdjan Djurovic (45, 91, 25) , Arne E. Vaaler (92, 93, 45) , Ole A. Andreassen (92, 44, 45) , Bernhard T. Baune (94, 95) , Tracy Air (96) , Martin Preisig (97, 98) , Rudolf Uher (84) , Douglas F. Levinson (99) , Myrna M. Weissman (100, 101) , James B. Potash (102) , Jianxin Shi (103) , James A. Knowles (41) , Roy H. Perlis (2) , Susanne Lucae (70) , Dorret I. Boomsma (104, 105) , Brenda W.J.H. Penninx (104) , Jouke-Jan Hottenga (104, 105) , Eco J.C. De Geus (104, 105) , Gonneke Willemsen (104, 105) , Yuri Milaneschi (104) , Henning Tiemeier (106) , Hans J. Grabe (107) , Alexander Teumer (107) , Sandra van Der Auwera (107) , Uwe Völker (107) , Steven P. Hamilton (108) , Patrik K.E. Magnusson (20) , Alexander Viktorin (20) , Divya Mehta (109) , Niamh Mullins (35) , Mark J. Adams (110) , Gerome Breen (111) , Andrew M. Mcintosh (110) , Cathryn M. Lewis (111) , David M. Hougaard (3, 112) , Merete Nordentoft (3, 113, 114) , Ole Mors (3, 115) , Preben B. Mortensen (4, 116) , Thomas Werge (114, 113) , Thomas D. Als (3, 4) , Anders D. Børglum (3, 4) , Tracey L. Petryshen (2, 117, 5, 23) , Jordan W. Smoller (2, 117, 5, 23) , Jill M. Goldstein (2, 118)
1 Maastricht University [Maastricht]
2 Massachusetts General Hospital [Boston]
3 iPSYCH - The Lundbeck Foundation Initiative for Integrative Psychiatric Research
4 Aarhus University [Aarhus]
5 BROAD INSTITUTE - Broad Institute of MIT and Harvard
6 YSM - Yale School of Medicine [New Haven, Connecticut]
7 CSU - Colorado State University [Fort Collins]
8 University of Aberdeen
9 Institute of Medical Sciences [Aberdeen, Royaume-Uni]
10 The Feinstein Institute for Medical Research
11 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
12 ZHH - Zucker Hillside Hospital [Glen Oaks, NY, USA]
13 Queensland Brain Institute
14 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
15 Schizophrenia Research Institute [Sydney]
16 UoN - University of Newcastle [Callaghan, Australia]
17 Cardiff University
18 Institute of Psychological Medicine and Clinical Neurosciences
19 Department of Genetics
20 Karolinska Institutet [Stockholm]
21 Trinity College Dublin
22 VCU - Virginia Commonwealth University
23 Stanley Center for Psychiatric Research [Cambridge, MA, USA]
24 University of Tartu
25 NORMENT - Norwegian Centre for Mental Disorders Research [Oslo]
26 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
27 MPI - Max Planck Institute of Experimental Medicine [Göttingen]
28 HKU Med - School of Public Health, Li Ka Shing Faculty of Medicine
29 HKU - The University of Hong Kong
30 Fujita Health University
31 LIBD - Lieber Institute for Brain Development [Baltimore]
32 Johns Hopkins University School of Medicine [Baltimore]
33 University of Chicago
34 North Shore University Hospital
35 MSSM - Icahn School of Medicine at Mount Sinai [New York]
36 University of Halle
37 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
38 UCL - University College of London [London]
39 Institute of Psychiatry, Psychology & Neuroscience, King's College London
40 SUNY Downstate Medical Center
41 USC - University of Southern California
42 Institute of Mental Health [Singapore]
43 Duke-National University of Singapore Graduate Medical School
44 UiO - University of Oslo
45 Oslo University Hospital [Oslo]
46 Diakonhjemmet Hospital
47 Rudolf Magnus Institute of Neuroscience
48 UC - University of California
49 Nus - Umeå University Hospital = Norrlands universitetssjukhus
50 QIMR Berghofer Medical Research Institute
51 NRA - Neuroscience Research Australia [Sydney, NSW, Australia]
52 UNSW - University of New South Wales [Sydney]
53 Philipps Universität Marburg = Philipps University of Marburg
54 University Hospital Bonn
55 AöR - University Hospital Essen
56 Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
57 IPPG - Institute of Psychiatric Phenomics and Genomics
58 Max Planck Institute for Psychological Research
59 ISGlobal - Instituto de Salud Global - Institute For Global Health [Barcelona]
60 IBIMA Plataforma BIONAND - Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina = Biomedical Research Institute of Málaga and Nanomedicine Platform
61 Frankfurt University Hospital
62 CACM, Medical Faculty Mannheim
63 Universität Heidelberg [Heidelberg] = Heidelberg University
64 Universität Bonn = University of Bonn
65 FZJ - Forschungszentrum Jülich GmbH | Centre de recherche de Jülich | Jülich Research Centre
66 ERA-LEARN - Prof. Dr. Alexandru Obregia Psychiatry Hospital
67 PUMS - Poznan University of Medical Sciences [Poland]
68 Maria Sklodowska-Curie National Research Institute of Oncology [Krakow, Poland]
69 University of Liverpool
70 Max Planck Institute of Psychiatry
71 NIOM - Nofer Institute of Occupational Medicine
72 SUNY Upstate Medical University
73 UMG - University Medical Center Göttingen
74 UC San Diego - University of California [San Diego]
75 UPE - Université Paris-Est
76 AP - HP - Hôpital Ambroise Paré , Assistance Publique - Hôpitaux de Paris
77 U955 Inserm - UPEC - IMRB - "Neuropsychiatrie translationnelle" [Créteil]
78 OPTeN (UMR_S 1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
79 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
80 Institute of Psychiatry, Psychology and Neuroscience - Department of Psychology [London, UK]
81 UPD7 - Université Paris Diderot - Paris 7
82 FondaMental Foundation
83 CAMH - Centre for Addiction and Mental Health [Toronto]
84 Dalhousie University [Halifax]
85 NIMH - National Institute of Mental Health [Klecany, Czech Republic]
86 MUHC - McGill University Health Center [Montreal]
87 Mayo Clinic [Rochester]
88 Lindner Center of HOPE [ Mason, USA]
89 University of Michigan [Ann Arbor]
90 Sahlgrenska Academy at University of Gothenburg [Göteborg]
91 UiB - University of Bergen
92 NTNU - Norwegian University of Science and Technology
93 St. Olav's University Hospital - St. Olavs Hospital HF
94 University of Melbourne
95 WWU - Westfälische Wilhelms-Universität Münster = University of Münster
96 University of Adelaide
97 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
98 UNIL - Université de Lausanne = University of Lausanne
99 Stanford University
100 Columbia University College of Physicians and Surgeons
101 New York State Psychiatric Institute
102 University of Iowa [Iowa City]
103 NCI-NIH - National Cancer Institute [Bethesda]
104 VU - Vrije Universiteit Amsterdam [Amsterdam]
105 Amsterdam Public Health Research Institute [The Netherlands]
106 Erasmus MC - Erasmus University Medical Center [Rotterdam]
107 University of Medicine Greifswald
108 Division of Research, Kaiser Permanente Northern California
109 QUT - Queensland University of Technology [Brisbane]
110 Edin. - University of Edinburgh
111 King‘s College London
112 Statens Serum Institut [Copenhagen]
113 Child and Adolescent Mental Health Center, Copenhagen University Hospital-Mental Health Services CPH, Copenhagen, Denmark.
114 UCPH - University of Copenhagen = Københavns Universitet
115 Aarhus University Hospital
116 National Centre for Register-based Research
117 HMS - Harvard Medical School [Boston]
118 Athinoula A. Martinos Center for Biomedical Imaging
Tracy Air
  • Fonction : Auteur

Résumé

Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10-6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10-7; rs73033497, p = 8.8 × 10-7; rs7914279, p = 6.4 × 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

Dates et versions

inserm-04617779 , version 1 (19-06-2024)

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Citer

Gabriëlla A.M. Blokland, Jakob Grove, Chia-Yen Chen, Chris Cotsapas, Stuart Tobet, et al.. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2021, 91 (1), pp.102-111. ⟨10.1016/j.biopsych.2021.02.972⟩. ⟨inserm-04617779⟩
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