White Matter Lesion Progression

Edith Hofer , Margherita Cavalieri (1) , Joshua C. Bis (2) , Charles Decarli (3) , Myriam Fornage (4, 5) , Sigurdur Sigurdsson (6, 7) , Velandai Srikanth (8, 9) , Stella Trompet (10) , Benjamin F.J. Verhaaren (11) , Chris Wolf , Qiong Yang (12) , Hieab H.H. Adams (13) , Philippe Amouyel (14) , Alex Beiser (15, 16) , Brendan M. Buckley , Michele Callisaya , Ganesh Chauhan (17) , Anton J.M. de Craen (18) , Carole Dufouil (19) , Cornelia M. van Duijn (11) , Ian Ford , Paul Freudenberger (20) , Rebecca F. Gottesman (21) , Vilmundur Gudnason (22, 23) , Gerardo Heiss (24) , Albert Hofman (11) , Thomas Lumley (25) , Oliver Martinez (26) , Bernard Mazoyer (27) , Chris Moran (28) , Wiro J. Niessen (11, 29) , Thanh Phan , Bruce M. Psaty (30, 2) , Claudia L. Satizabal (31) , Naveed Sattar (32) , Sabrina Schilling (33) , Dean K. Shibata (34) , P. Eline Slagboom (35) , Albert Smith , David J. Stott (36) , Kent D. Taylor , Russell Thomson , Anna M. Töglhofer (1) , Christophe Tzourio (19) , Mark van Buchem (37) , Jing Wang (38) , Rudi G.J. Westendorp (39, 40) , B. Gwen Windham , Meike W. Vernooij (41, 42) , Alex Zijdenbos (43) , Richard Beare (8, 44) , Stéphanie Debette (19) , M. Arfan Ikram (11, 45) , J. Wouter Jukema (10) , Lenore J. Launer , W. T. Longstreth (2) , Thomas H. Mosley (46) , Sudha Seshadri (47) , Helena Schmidt (48) , Reinhold Schmidt

1 Medical University of Graz
2 University of Washington [Seattle]
3 Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento
4 Human Genetics Center
5 UTHealth - The University of Texas Health Science Center at Houston
6 Department of Medical Biochemistry and Microbiology
7 Broad Institute [Cambridge]
8 Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University
9 Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia
10 Interuniversity Cardiology Institute Netherlands
11 Erasmus MC - Erasmus University Medical Center [Rotterdam]
12 Anhui University [Hefei]
13 Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique
14 Université de Lille
15 BU - Boston University [Boston]
16 BUSM - Boston University School of Medicine
17 INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France
18 Department of neurology
19 Epidémiologie et Biostatistique [Bordeaux]
20 Institute of Molecular Biology & Biochemistry
21 Johns Hopkins University School of Medicine [Baltimore]
22 Icelandic Heart Association, Kopavogur, Iceland.
23 Faculty of Medicine
24 UNC - University of North Carolina [Chapel Hill]
25 Department of Biostatistics, University of Washington
26 IPBS - Institut de pharmacologie et de biologie structurale
27 GIN - UMR 5296 - Groupe d'Imagerie Neurofonctionnelle
28 Wellcome Trust - MRC Cambridge
29 TU Delft - Delft University of Technology
30 Group Health Research Institute, Group Health Cooperative
31 INSERM, Neuroepidemiology U708, Bordeaux, France
32 Department of Pathological Biochemistry
33 Department for Internal Medicine
34 Department of Radiology, University of Washington
35 Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands Consortium for Healthy Aging, Leiden University Medical Center, Leiden, the Netherlands
36 Institute of Cardiovascular and Medical Sciences [Glasgow]
37 Department of Radiology [Leiden, The Netherlands]
38 LENSIS - Laboratoire d'Etude des NanoStructures et Imagerie de Surface
39 Department of Gerontology and Geriatrics
40 Netherlands Consortium for Healthy Ageing
41 Department of Neurology [Rotterdam]
42 Departments of Radiology and of Epidemiology [Rotterdam]
43 Biospective [Montréal]
44 MCRI - Murdoch Children's Research Institute
45 Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands
46 UMMC - University of Mississippi Medical Center
47 Department of Neurology [Boston, USA]
48 Dpt of Pharmacology and Personalised Medicine [Maastricht]

Background and Purpose—White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Methods—Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies. Results—A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (P<5×10−8). Four loci were suggestive (P<1×10−5) of an association with WML progression: 10q24.32 (rs10883817, P=1.46×10−6); 12q13.13 (rs4761974, P=8.71×10−7); 20p12.1 (rs6135309, P=3.69×10−6); and 4p15.31 (rs7664442, P=2.26×10−6). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden. Conclusions—Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors.

Mots clés: biological factors; cerebral small vessel diseases; magnetic resonance imaging; white matter lesions; aging

Domaines: Neurosciences

Edith Hofer, Margherita Cavalieri, Joshua C. Bis, Charles Decarli, Myriam Fornage, et al.. White Matter Lesion Progression. Stroke, 2015, 46 (11), pp.3048 - 3057. ⟨10.1161/STROKEAHA.115.009252⟩. ⟨hal-01379523⟩