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Article Dans Une Revue Nature Communications Année : 2020

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Edith Hofer (1, 2) , Gennady V. Roshchupkin (3) , Hieab H. H. Adams (3) , Maria J. Knol (3) , Honghuang Lin (4) , Shuo Li (5) , Habil Zare (6, 7) , Shahzad Ahmad (3) , Nicola J. Armstrong (8) , Claudia L. Satizabal (7, 4) , Manon Bernard (9) , Joshua C. Bis (10) , Nathan A. Gillespie (11, 12) , Michelle Luciano (13) , Aniket Mishra (14) , Markus Scholz (15) , Alexander Teumer (16) , Rui Xia (17) , Xueqiu Jian (17) , Thomas H. Mosley (18) , Yasaman Saba (2) , Lukas Pirpamer (2) , Stephan Seiler (19) , James T. Becker (20) , Owen Carmichael (21) , Jerome I. Rotter (22) , Bruce M. Psaty (10) , Oscar L. Lopez (20) , Najaf Amin (3) , Sven J. van Der Lee (3) , Qiong Yang (5) , Jayandra J. Himali (5) , Pauline Maillard (19) , Alexa S. Beiser (5, 4) , Charles Decarli (19) , Sherif Karama (23) , Lindsay Lewis (23) , Mat Harris (13) , Mark E. Bastin (13) , Ian J. Deary (13) , A. Veronica Witte (24, 15) , Frauke Beyer (24, 15) , Markus Loeffler (15) , Karen A. Mather (25, 26) , Peter R. Schofield (26, 25) , Anbupalam Thalamuthu (25) , John B. Kwok (25, 27) , Margaret J. Wright (28) , David Ames (29, 30) , Julian Trollor (25) , Jiyang Jiang (25) , Henry Brodaty (25) , Wei Wen (25) , Meike W. Vernooij (3) , Albert Hofman (31, 3) , André G. Uitterlindin (3) , Wiro J. Niessen (32, 3) , Katharina Wittfeld (33, 16) , Robin Bülow (16) , Uwe Völker (16) , Zdenka Pausova (9, 34) , G. Bruce Pike (35) , Sophie Maingault (36) , Fabrice Crivello (36) , Christophe Tzourio (14, 37) , Philippe Amouyel (38, 39, 40) , Bernard Mazoyer (36) , Michael C. Neale (11) , Carol E. Franz (41) , Michael J. Lyons (42) , Matthew S. Panizzon (41) , Ole A. Andreassen (43, 44) , Anders M. Dale (41) , Mark Logue (5, 45, 4) , Katrina L. Grasby (12) , Neda Jahanshad (46) , Jodie N. Painter (12) , Lucía Colodro-Conde (12) , Janita Bralten (47, 48) , Derrek P. Hibar (46, 49) , Penelope A. Lind (12) , Fabrizio Pizzagalli (46) , Jason L. Stein (50) , Paul M. Thompson (46) , Sarah E. Medland (12) , Enigma Consortium , Perminder S. Sachdev (25, 51) , William S. Kremen (41) , Joanna M. Wardlaw (13) , Arno Villringer (24, 52) , Cornelia M. van Duijn (3, 53) , Hans J. Grabe (33, 16) , William T. Longstreth Jr. (10) , Myriam Fornage (17) , Tomas Paus (54, 34) , Stéphanie Debette (4, 14, 37) , M. Arfan Ikram (3) , Helena Schmidt (2) , Reinhold Schmidt (2) , Sudha Seshadri (7, 4)
1 Karl-Franzens-Universität Graz
2 Medical University Graz
3 Erasmus MC - Erasmus University Medical Center [Rotterdam]
4 BUSM - Boston University School of Medicine
5 School of Public Health [Boston]
6 University of Texas Health Science Center
7 UTSA - The University of Texas at San Antonio
8 Murdoch University
9 SickKids - The Hospital for sick children [Toronto]
10 University of Washington [Seattle]
11 VCU - Virginia Commonwealth University
12 QIMR Berghofer Medical Research Institute
13 Edin. - University of Edinburgh
14 BPH - Bordeaux population health
15 Leipzig University / Universität Leipzig
16 Universität Greifswald - University of Greifswald
17 UTHealth - The University of Texas Health Science Center at Houston
18 UMMC - University of Mississippi Medical Center
19 UC Davis - University of California [Davis]
20 PITT - University of Pittsburgh
21 Pennington Biomedical Research Center
22 LA BioMed - Los Angeles Biomedical Research Institute
23 McGill University = Université McGill [Montréal, Canada]
24 IMPNSC - Max Planck Institute for Human Cognitive and Brain Sciences [Leipzig]
25 UNSW - University of New South Wales [Sydney]
26 NeuRA - Neuroscience Research Australia
27 The University of Sydney
28 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
29 The Royal Melbourne Hospital
30 University of Melbourne
31 Harvard T.H. Chan School of Public Health
32 TU Delft - Delft University of Technology
33 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
34 University of Toronto
35 University of Calgary
36 IMN - Institut des Maladies Neurodégénératives [Bordeaux]
37 CHU Bordeaux
38 RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167
39 Institut Pasteur de Lille
40 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
41 UC San Diego - University of California [San Diego]
42 BU - Boston University [Boston]
43 UiO - University of Oslo
44 Oslo University Hospital [Oslo]
45 VA Boston Healthcare System
46 USC - University of Southern California
47 Radboud University Medical Center [Nijmegen]
48 Radboud University [Nijmegen]
49 Janssen Research & Development
50 UNC - University of North Carolina [Chapel Hill]
51 Prince of Wales Hospital
52 University Hospital Leipzig = Universitätsklinikum Leipzig
53 University of Oxford
54 Holland Bloorview Kids Rehabilitation Hospital [Toronto, ON, Canada]
Christophe Tzourio
Enigma Consortium
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Reinhold Schmidt
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Résumé

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
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hal-03150306 , version 1 (23-02-2021)

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Edith Hofer, Gennady V. Roshchupkin, Hieab H. H. Adams, Maria J. Knol, Honghuang Lin, et al.. Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults. Nature Communications, 2020, 11, pp.4796. ⟨10.1038/s41467-020-18367-y⟩. ⟨hal-03150306⟩
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