Common variants at 12q14 and 12q24 are associated with hippocampal volume. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nature Genetics Année : 2012

Common variants at 12q14 and 12q24 are associated with hippocampal volume.

Joshua C Bis (1) , Charles Decarli (2, 3) , Albert Vernon Smith (4, 5) , Fedde van Der Lijn (6) , Fabrice Crivello (7) , Myriam Fornage (8, 9) , Stephanie Debette (10, 11) , Joshua M Shulman (12, 13) , Helena Schmidt (14) , Velandai Srikanth (15, 16) , Maaike Schuur (6) , Lei Yu (17) , Seung-Hoan Choi (18) , Sigurdur Sigurdsson (4) , Benjamin F J Verhaaren (6) , Anita L Destefano (11, 18, 19) , Jean-Charles Lambert (20, 21) , Clifford R Jack (22) , Maksim Struchalin (6) , Jim Stankovich (16) , Carla A Ibrahim-Verbaas (6) , Debra Fleischman (17, 22) , Alex Zijdenbos (23) , Tom den Heijer (6, 24) , Bernard Mazoyer (7) , Laura H Coker (25) , Christian Enzinger (26) , Patrick Danoy (27) , Najaf Amin (6) , Konstantinos Arfanakis (17, 28) , Mark A van Buchem (29) , Renée F a G de Bruijn (6) , Alexa Beiser (11, 18, 19) , Carole Dufouil (10) , Juebin Huang (30) , Margherita Cavalieri (26) , Russell Thomson (16) , Wiro J Niessen (6, 31) , Lori B Chibnik (12, 13) , Gauti K Gislason (4) , Albert Hofman (6, 32) , Aleksandra Pikula (11) , Philippe Amouyel (21, 20, 33) , Kevin B Freeman (30) , Thanh G Phan (15) , Ben A Oostra (6) , Jason L Stein (34) , Sarah E Medland (35, 36) , Alejandro Arias Vasquez (37, 38) , Derrek P Hibar (34) , Margaret J Wright (35) , Barbara Franke (37, 38) , Nicholas G Martin (35) , Paul M Thompson (34) , Michael A Nalls (39) , Andre G Uitterlinden (32, 6) , Rhoda Au (11, 19) , Alexis Elbaz (10, 40) , Richard J Beare (15, 41) , John C van Swieten (6) , Oscar L Lopez (42) , Tamara B Harris (39) , Vincent Chouraki (21, 20) , Monique M B Breteler (43, 44) , Philip L de Jager (12, 13, 45) , James T Becker (42) , Meike W Vernooij (6) , David Knopman (46) , Franz Fazekas (26) , Philip A Wolf (11, 19) , Aad van Der Lugt (6) , Vilmundur Gudnason (4, 5) , W T Longstreth (1) , Matthew A Brown (47) , David A Bennett (17) , Cornelia M van Duijn (6, 32, 48) , Thomas H Mosley (30) , Reinhold Schmidt (26) , Christophe Tzourio (49, 50) , Lenore J Launer (38) , M Arfan Ikram (6, 32) , Sudha Seshadri (11, 19)
1 University of Washington [Seattle]
2 UC Davis - University of California [Davis]
3 Center for Neuroscience
4 Icelandic Heart Association, Kopavogur, Iceland.
5 Faculty of Medicine
6 Erasmus MC - Erasmus University Medical Center [Rotterdam]
7 GIN - UMR 5296 - Groupe d'Imagerie Neurofonctionnelle
8 UTHealth - The University of Texas Health Science Center at Houston
9 Human Genetics Center
10 Institut National de la Santé et de la Recherche Médicale (INSERM), U708, Neuroepidemiology, Paris, France
11 BUSM - Boston University School of Medicine
12 Program in Translational NeuroPsychiatric Genomics,
13 Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
14 Institute of Molecular Biology and Biochemistry
15 Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University
16 Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia
17 Rush University Medical Center [Chicago]
18 BU - Boston University [Boston]
19 Framingham Heart Study
20 Université Lille Nord de France (COMUE)
21 Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations
22 Department of Radiology
23 Biospective [Montréal]
24 Department of Neurology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands
25 Wake Forest School of Medicine [Winston-Salem]
26 Department of Neurology, Medical University Graz, Graz, Austri
27 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
28 Department of Biomedical Engineering
29 Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
30 UMMC - University of Mississippi Medical Center
31 TU Delft - Delft University of Technology
32 Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands
33 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
34 David Geffen School of Medicine [Los Angeles]
35 Queensland Institute of Medical Research
36 BROAD INSTITUTE - Broad Institute of MIT and Harvard
37 Department of Human Genetics [Nijmegen]
38 Donders Institute for Brain, Cognition and Behaviour
39 NIH - National Institutes of Health [Bethesda, MD, USA]
40 CHU Pitié-Salpêtrière [AP-HP]
41 MCRI - Murdoch Children's Research Institute
42 University of Pittsburgh School of Medicine
43 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
44 Harvard University
45 HMS - Harvard Medical School [Boston]
46 Mayo Clinic [Rochester]
47 Human Genetics Group, University of Queensland Diamantina Institute, Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia
48 Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands
49 University of Bordeaux, U708, Bordeaux, France
50 INSERM, Neuroepidemiology U708, Bordeaux, France
Fabrice Crivello
Bernard Mazoyer

Résumé

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7). In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.

Domaines

Neurosciences

Dates et versions

hal-01157821 , version 1 (01-06-2015)

Identifiants

Citer

Joshua C Bis, Charles Decarli, Albert Vernon Smith, Fedde van Der Lijn, Fabrice Crivello, et al.. Common variants at 12q14 and 12q24 are associated with hippocampal volume.. Nature Genetics, 2012, 44 (5), pp.545-551. ⟨10.1038/ng.2237⟩. ⟨hal-01157821⟩
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