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Article Dans Une Revue Nature Communications Année : 2019

A meta-analysis of genome-wide association studies identifies multiple longevity genes

Joris Deelen (1, 2) , Daniel Evans (3) , Dan E. Arking (4, 5) , Niccolò Tesi (6, 7, 8) , Marianne Nygaard (9) , Xiaomin Liu (10, 11) , Mary Wojczynski (12) , Mary Biggs (13, 14) , Ashley van Der Spek (15) , Gil Atzmon (16, 17) , Erin Ware (18) , Chloé Sarnowski (19) , Albert Smith (20, 21) , Ilkka Seppälä (22) , Heather J. Cordell (23) , Janina Dose (24) , Najaf Amin (25) , Alice Arnold (26) , Kristin Ayers (25) , Nir Barzilai (16) , Elizabeth Becker (27) , Marian Beekman (2) , Hélène Blanché (28) , Kaare Christensen (9, 29) , Lene Christiansen (9, 30) , Joanna Collerton (31) , Sarah Cubaynes (32) , Steven Cummings (3) , Karen Davies (33) , Birgit Debrabant (34) , Jean-François Deleuze (28, 35) , Rachel Duncan (36, 37) , Jessica Faul (38) , Claudio Franceschi (39, 40) , Pilar Galan (41) , Vilmundur Gudnason (42, 43) , Tamara B. Harris (44) , Martijn Huisman (45, 46) , Mikko Hurme (47) , Carol Jagger (48, 49, 50) , Iris Jansen (6, 51) , Marja Jylhä (52) , Mika Kähönen (53) , David Karasik (53) , Sharon Kardia (54) , Andrew Kingston (31, 37) , Thomas Kirkwood (37) , Lenore Launer (44) , Terho Lehtimäki (55) , Wolfgang Lieb (56) , Leo-Pekka Lyytikäinen (57) , Carmen Martin-Ruiz (33) , Junxia Min (58) , Almut Nebel (24) , Anne Newman (59) , Chao Nie (10) , Ellen Nohr (9) , Eric Orwoll (60) , Thomas Perls (61) , Michael Province (12) , Bruce Psaty (62, 63, 64, 65) , Olli Raitakari (53, 66) , Marcel Reinders (8) , Jm Robine (32, 67) , Jerome Rotter (68, 69) , Paola Sebastiani (19) , Jennifer Smith (70) , Thorkild I. A. Sørensen (71, 72) , Kent D Taylor (73, 74) , André G. Uitterlinden (75, 15, 76) , Wiesje van Der Flier (77, 45) , Sven van Der Lee (6, 7) , Cornelia M. van Duijn (15, 78) , Diana van Heemst (2) , James Vaupel (79) , David Weir (70) , Kenny Ye (80) , Yi Zeng (81, 82) , Wanlin Zheng (3) , Henne Holstege (83, 7, 8) , Douglas Kiel (84, 85, 86) , Kathryn Lunetta (27) , P. Eline Slagboom (2) , Joanne Murabito (27, 61)
1 Max planck Institute for Biology of Ageing [Cologne]
2 LUMC - Leiden University Medical Center
3 California Pacific Medical Center Research Institute
4 Johns Hopkins University School of Medicine [Baltimore]
5 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
6 Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam
7 Department of Clinical Genetics (Academic Medical Center, University of Amsterdam)
8 Delft Bioinformatics Lab [Delft]
9 SDU - University of Southern Denmark
10 BGI - Beijing Genomics Institute [Shenzhen]
11 China National GeneBank
12 Division of Statistical Genomics
13 Department of Biostatistics
14 Department of Medicine
15 Department of Epidemiology [Rotterdam]
16 Department of Medicine [Bronx, NY, USA]
17 Department of Biology, Faculty of Sciences and Science Education, Haifa University
18 Institute for Social Research
19 Department of Biostatistics [Boston, MA, USA]
20 IHA - Icelandic Heart Association [Kopavogur, Iceland]
21 Department of Biostatistics
22 Department of Clinical Chemistry
23 Institute of Genetic Medicine [Newcastle]
24 Institute of Clinical Molecular Biology
25 SEMA4
26 Department of Biostatistics, University of Washington
27 BU - Boston University [Boston]
28 Fondation Jean Dausset CEPH
29 Odense University Hospital, Odense
30 Copenhagen University Hospital
31 Institute of Health and Society
32 MMDN - Mécanismes moléculaires dans les démences neurodégénératives
33 ION - Institute of Neuroscience [Newcastle]
34 Institute of Clinical Research
35 CNG - Centre National de Génotypage
36 Institute of Health and Society
37 Institute of Ageing and Health, Newcastle University, Newcastle Upon Tyne
38 Institute for Social Research
39 Department of Applied Mathematics and Centre of Bioinformatics,
40 Institute of Neurological Sciences of Bologna IRCCS
41 CRESS - U1153 - Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle
42 Icelandic Heart Association
43 University of Iceland [Reykjavik]
44 NIA - National Institute on Aging [Bethesda, USA]
45 Department of Clinical Epidemiology and Biostatistics, VU Medical Centre, Amsterdam
46 Amsterdam Public Health Research Institute [The Netherlands]
47 Department of Microbiology and Immunology
48 Newcastle University [Newcastle]
49 Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne
50 Institute of Health & Society
51 Department of Complex Trait Genetics
52 University of Tampere [Finland]
53 Tampere University Hospital
54 School of Public Health
55 Faculty of Medicine and Life Sciences [Tampere]
56 Institute of Epidemiology and Biobank PopGen
57 Faculty of Medicine and Health Technology [Tampere, Finland]
58 Zhejiang University School of Medicine [China]
59 University of Pittsburgh Graduate School of Public Health
60 Oregon Health & Sciences University
61 BUSM - Boston University School of Medicine
62 University of Washington [Seattle]
63 Department of Medicine, University of Washington
64 Department of Epidemiology, University of Washington
65 KPWHRI - Kaiser Permanente Washington Health Research Institute [Seattle]
66 TYKS - Turku University Hospital
67 University of Turku
68 School of Medicine [Los Angeles]
69 UCLA Medical Center
70 University of Michigan [Ann Arbor]
71 University of Copenhage, Faculty of Health and Medical Sciences
72 MRC IEU - MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni]
73 LA BioMed - Los Angeles Biomedical Research Institute
74 Harbor UCLA Medical Center [Torrance, Ca.]
75 Netherlands Genomics Initiative
76 ROTTERDAM - Med Int - Department of Internal Medicine
77 Alzheimercentre, department of Neurology, VU University Medical Center
78 Nuffield Department of Population Health [Oxford]
79 MPIDR - Max Planck Institute for Demographic Research
80 Albert Einstein College of Medicine [New York]
81 Beijing Forestry University
82 Medical School of Duke University
83 Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam
84 Hinda and Arthur Marcus Institute for Aging Research,Hebrew SeniorLife
85 HMS - Harvard Medical School [Boston]
86 Broad Institute of MIT & Harvard
Najaf Amin
  • Fonction : Auteur
Kristin Ayers
  • Fonction : Auteur
Hélène Blanché
Mikko Hurme
  • Fonction : Auteur
  • PersonId : 907681
Mika Kähönen
Almut Nebel
  • Fonction : Auteur
  • PersonId : 910303
Michael Province
  • Fonction : Auteur
  • PersonId : 909651
Diana van Heemst
  • Fonction : Auteur
  • PersonId : 889897

Résumé

A meta-analysis of genome-wide association studies identifies multiple longevity genes Joris Deelen et al. # Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
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hal-02530209 , version 1 (02-04-2020)

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Joris Deelen, Daniel Evans, Dan E. Arking, Niccolò Tesi, Marianne Nygaard, et al.. A meta-analysis of genome-wide association studies identifies multiple longevity genes. Nature Communications, 2019, 10 (1), ⟨10.1038/s41467-019-11558-2⟩. ⟨hal-02530209⟩
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