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White matter lesion progression: genome-wide search for genetic influences


Hofer, E and Cavalieri, M and Bis, JC and DeCarli, C and Fornage, M and Sigurdsson, S and Srikanth, V and Trompet, S and Verhaaren, BFJ and Wolf, C and Yang, Q and Adams, HHH and Amouyel, P and Beiser, A and Buckley, BM and Callisaya, M and Chauhan, M and de Craen, AJM and Dufouil, C and van Dujin, CM and Ford, I and Freudenberger, P and Gottesman, RF and Gudnason, V and Heiss, G and Hofman, A and Lumley, T and Martinez, O and Mazoyer, B and Moran, C and Niessen, WJ and Phan, T and Psaty, BM and Satizabal, CL and Sattar, N and Schilling, S and Shibata, DK and Slagboom, PE and Smith, A and Stott, DJ and Taylor, KD and Thomson, R and Toglhoger, AM and Tzourio, C and van Buchem, M and Wang, J and Westendorp, RGJ and Windham, BG and Vernooij, MW and Zijdenbos, A and Beare, R and Debette, S and Ikram, MA and Jukema, JW and Launer, LJ and Longstreth Jr, WT and Mosley, TH and Seshadri, S and Schmidt, H and Schmidt, R, Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, White matter lesion progression: genome-wide search for genetic influences, Stroke, 46, (11) pp. 3048-3057. ISSN 0039-2499 (2015) [Refereed Article]

Copyright Statement

2015 American Heart Association, Inc.

DOI: doi:10.1161/STROKEAHA.115.009252


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<5נ10−8). Four loci were suggestive (P<1נ10−5) of an association with WML progression: 10q24.32 (rs10883817, P=1.46נ10−6); 12q13.13 (rs4761974, P=8.71נ10−7); 20p12.1 (rs6135309, P=3.69נ10−6); and 4p15.31 (rs7664442, P=2.26נ10−6). 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.

Item Details

Item Type:Refereed Article
Keywords:white matter hyperintensities, genetics, aging, biological factors, cerebral small vessel diseases, magnetic resonance imaging, white matter lesions
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Geriatrics and gerontology
Objective Division:Health
Objective Group:Specific population health (excl. Indigenous health)
Objective Field:Health related to ageing
UTAS Author:Srikanth, V (Dr Velandai Srikanth)
UTAS Author:Callisaya, M (Dr Michele Callisaya)
UTAS Author:Thomson, R (Dr Russell Thomson)
ID Code:104288
Year Published:2015
Web of Science® Times Cited:17
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-11-06
Last Modified:2017-11-01

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